Centre for Nanosciences
Amrita Institute of Medical Sciences,
Amrita Vishwa Vidyapeetham
AIMS Ponekkara P. O., Kochi, Kerala - 682 041, India.

0484 285 8750
researchsecretary@aims.amrita.edu
 

 

Research & Projects

Research at ACNSMM includes development of disease specific nanomedicines, identification of molecular markers for clinical conditions, designing novel delivery systems for use in wound healing, nervous system, cardiovascular ailments, and many others. The department also has a strong bioinformatics unit, along with 3D bioprinting , stem cell program, and tissue regeneration laboratories. Parallelly, the center also houses the Renewable and Energy storage division that focuses on research that supports generation of clean and sustainable forms of energy.

Amrita Center for Nanosciences has several common facilities to aid research labs conduct work related to their specialities.

Nano-characterisation Facility

The lab is equipped with FTIR, UV-VIS Spectrophotometer, Spectrofuorimeter, Thermal Analysis Systems (DSC, TGA/DTA) and Particle Sizer with Zeta Potential Analyser for physiochemical characterization of nanomaterials.

Cell Culture & Stem Cell Facility

The lab is equipped with Cell/ Stem Cell/ Tissue Culture Facility with Biological Safety Cabinets, CO2 Incubator, Inverted Microscope, Fluorescent Microscope, Liquid N2 Facility, - 80°C freezer, -20°C freezer, etc.

High-resolution Imaging Facility

The lab has state-of-the-art microscopes including a high resolution Scanning Electron microscope, Atomic Force microscope and Fluorescence microscope. Other additions to the lab include the new generation Spectral Confocal Laser Scanning microscope and the transmission electron microscope.

Nanotoxicology Facility

The lab is equipped with a non-invasive, whole animal multispectral imaging system having fluorescence and X - ray imaging capabilities.

Nanochemistry and Electrospinning Facility

The lab is equipped for wet chemical processing of various types of nanomaterials such as inorganic, metallic and polymeric nanoparticles. An electrospinning set-up is also available for developing nanofibrous scaffolds and structures.

Flow Cytometry and Cell Sorting Facility

The FACS lab is equipped to handle both, clinical and research samples. Currently, it is equipped with two flow cytometers and is one of the heavily used services.

Publications

Publication Type: Journal Article

Year of Publication Publication Type Title

2019

Journal Article

A. C. P, Subhramanian, S., Sizochenko, N., Melge, A. R., Leszczynski, J., and C Mohan, G., “Multiple e-Pharmacophore modeling to identify a single molecule that could target both streptomycin and paromomycin binding sites for 30S ribosomal subunit inhibition.”, J Biomol Struct Dyn, vol. 37, no. 6, pp. 1582-1596, 2019.[Abstract]


<p>The bacterial ribosome is an established target for anti-bacterial therapy since decades. Several inhibitors have already been developed targeting both defined subunits (50S and 30S) of the ribosome. Aminoglycosides and tetracyclines are two classes of antibiotics that bind to the 30S ribosomal subunit. These inhibitors can target multiple active sites on ribosome that have a complex structure. To screen putative inhibitors against 30S subunit of the ribosome, the crystal structures in complex with various known inhibitors were analyzed using pharmacophore modeling approach. Multiple active sites were considered for building energy-based three-dimensional (3D) pharmacophore models. The generated models were validated using enrichment factor on decoy data-set. Virtual screening was performed using the developed 3D pharmacophore models and molecular interaction towards the 30S ribosomal unit was analyzed using the hits obtained for each pharmacophore model. The hits that were common to both streptomycin and paromomycin binding sites were identified. Further, to predict the activity of these hits a robust 2D-QSAR model with good predictive ability was developed using 16 streptomycin analogs. Hence, the developed models were able to identify novel inhibitors that are capable of binding to multiple active sites present on 30S ribosomal subunit.</p>

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2019

Journal Article

S. Padmakumar, Paul-Prasanth, B., Pavithran, K., Vijaykumar, D. K., Rajanbabu, A., Sivanarayanan, T. B., Kadakia, E., Amiji, M. M., Shantikumar V Nair, and Menon, D., “Long-term drug delivery using implantable electrospun woven polymeric Nanotextiles.”, Nanomedicine, 2019.[Abstract]


A woven nanotextile implant was developed and optimized for long-term continuous drug delivery for potential oncological applications. Electrospun polydioxanone (PDS) nanoyarns, which are twisted bundles of PDS nanofibres, were loaded with paclitaxel (PTX) and woven into nanotextiles of different packing densities. A mechanistic modeling of in vitro drug release proved that a combination of diffusion and matrix degradation controlled the slow PTX-release from a nanoyarn, emphasizing the role of nanostructure in modulating release kinetics. Woven nanotextiles, through variations in its packing density and thereby architecture, demonstrated tuneable PTX-release. In vivo PTX-release, pharmacokinetics and biodistribution were evaluated in healthy BALB/c mice by suturing the nanotextile to peritoneal wall. The slow and metronomic PTX-release for 60days from the loosely woven implant was extremely effective in enhancing its residence in peritoneum, in contrast to intraperitoneal injections. Such an implantable matrix offers a novel platform for therapy of solid tumors over prolonged durations.

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2019

Journal Article

S. Xavier, Dr. Gopi Mohan C., Shantikumar V Nair, Krishnakumar N. Menon, and Dr. Lakshmi Sumitra, “Generation of Humanized Single-chain Fragment Variable Immunotherapeutic against EGFR Variant III using Baculovirus Expression System and in vitro validation.”, Int J Biol Macromol, vol. 124, pp. 17-24, 2019.[Abstract]


Epidermal growth factor receptor variant III (EGFRvIII) is known to be specifically expressed in cancer cells and associated with tumor virulence. The receptor provides an opportunity for both specifically targeting the tumor cells as well as for potentially controlling and inhibiting tumor progression. In this study, humanized anti-EGFRvIII single-chain fragment variable (hscFv) was expressed in insect cell culture system to accommodate post-translational glycosylations crucial for the fragment stability and efficacy. Target specific binding of the developed fragment to EGFRvIII expressing cell lines and EGFRvIII positive glioblastoma patient samples was evaluated by immunocytochemistry and immunohistochemistry respectively. Downstream intracellular signaling mechanisms related to the action of the developed antibody fragment on growth/metabolism of the cell was evaluated in U87-EGFRvIII human glioblastoma cell lines. It was observed that the hscFv bound specifically to EGFRvIII in mutant expressing cells. Functionally, hscFv was found to confer anti-proliferative properties in EGFRvIII expressing cell lines by downregulating phosphorylation of EGFR/EGFRvIII, Lyn, PI3K and GLUT3 involved in proliferation and metabolism. This study demonstrated the significance of hscFv as a potential immunotherapeutic agent as well as a targeting agent for specific delivery of drugs to EGFRvIII expressing cancer cells.

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2019

Journal Article

P. Rajitha, Shammika, P., S. Aiswarya, Gopikrishnan, A., Dr. Jayakumar Rangasamy, and Sabitha, M., “Chaulmoogra oil based Methotrexate Loaded Topical Nanoemulsion for the Treatment of Psoriasis”, Journal of Drug Delivery Science and Technology, vol. 49, pp. 463 - 476, 2019.[Abstract]


Chaulmoogra oil based methotrexate loaded nanoemulsion was prepared via emulsification technique using tween 80 and ethanol as surfactants. The formulation was characterized by FTIR and TEM. The prepared nanoemulsion has an average particle size of 34 nm with negative surface charge and has pH compatible to skin. Rheological studies revealed the shear thinning non-Newtonian visco-elastic behavior of the formulation as explained by the Herschel Bulkley model. The formulation was cytocompatible towards mouse dermal fibroblast L929 cells when tested by MTT assay and was stable in refrigerator for the tested period of 3 months. The in-vitro release mechanism of methotrexate from formulation followed zero order release kinetics with non Fickian diffusion mechanism. The ex-vivo skin permeation studies done by Franz diffusion cell apparatus using porcine skin revealed the improved skin permeation and retention of drug in deep skin layers when compared with control drug solution. The in vivo anti-psoriatic studies done on imiquimod psoriatic model revealed superior anti-psoriatic efficacy, with effective skin retention and lesser serum and tissue accumulation when compared with orally administered methotrexate tablet.

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2019

Journal Article

R. Yegappan, Selvaprithiviraj, V., Amirthalingam, S., Mohandas, A., Hwang, N. S., and Dr. Jayakumar Rangasamy, “Injectable Angiogenic and Osteogenic Carrageenan Nanocomposite Hydrogel for Bone Tissue Engineering”, International Journal of Biological Macromolecules, vol. 122, pp. 320 - 328, 2019.[Abstract]


Functional biomaterials that couple angiogenesis and osteogenesis processes are vital for bone tissue engineering and bone remodeling. Herein we developed an injectable carrageenan nanocomposite hydrogel incorporated with whitlockite nanoparticles and an angiogenic drug, dimethyloxallylglycine. Synthesized whitlockite nanoparticles and nanocomposite hydrogels were characterized using SEM, TEM, EDS and FTIR. Developed hydrogels were injectable, mechanically stable, cytocompatible and has better protein adsorption. Incorporation of dimethyloxallylglycine resulted in initial burst release followed by sustained release for 7 days. Human umbilical vein endothelial cells exposed to dimethyloxallylglycine incorporated nanocomposite hydrogel showed enhanced cell migration and capillary tube-like structure formation. Osteogenic differentiation in rat adipose derived mesenchymal stem cells after 7 and 14 days revealed increased levels of alkaline phosphatase activity in vitro. Furthermore, cells exposed to nanocomposite hydrogel revealed enhanced protein expressions of RUNX2, COL and OPN. Overall, these results suggest that incorporation of whitlockite and dimethyloxallylglycine in carrageenan hydrogel promoted osteogenesis and angiogenesis in vitro.

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2019

Journal Article

Girish C. M., Dr. Subramania Iyer K., Dr. Krishnakumar T., GS, G., Dr. Manzoor K., and Shantikumar V Nair, “A Novel Surface Enhanced Raman Catheter for Rapid Detection, Classification, and Grading of Oral Cancer”, Advanced Healthcare Materials, vol. 13:e1801557, 2019.[Abstract]


Fabrication and testing of a novel nanostructured surface-enhanced Raman catheter device is reported for rapid detection, classification, and grading of normal, premalignant, and malignant tissues with high sensitivity and accuracy. The sensor part of catheter is formed by a surface-enhanced Raman scattering (SERS) substrate made up of leaf-like TiO2 nanostructures decorated with 30 nm sized Ag nanoparticles. The device is tested using a total of 37 patient samples wherein SERS signatures of oral tissues consisting of malignant oral squamous cell carcinoma (OSCC), verrucous carcinoma, premalignant leukoplakia, and disease-free conditions are detected and classified with an accuracy of 97.24% within a short detection-cum-processing time of nearly 25-30 min per patient. Neoplastic grade changes detected using this device correlate strongly with conventional pathological data, enabling correct classification of tumors into three grades with an accuracy of 97.84% in OSCC. Thus, the potential of a SERS catheter device as a point-of-care pathological tool is shown for the rapid and accurate detection, classification, and grading of solid tumors.

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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2018

Journal Article

M. Chatterjee, Pushkaran, A. Choorakott, Vasudevan, A. Kumar, Menon, K. Kumar N., Biswas, R., and Mohan, C. Gopi, “Understanding the adhesion mechanism of a mucin binding domain from Lactobacillus fermentum and its role in enteropathogen exclusion.”, Int J Biol Macromol, vol. 110, pp. 598-607, 2018.[Abstract]


<p>Lactobacillus species possesses surface exposed Mucin Binding Protein (MucBP) which plays a role in adhesion to gastrointestinal mucin. MucBP contains one or more mucin binding domain (MBD), the functionality of which has yet not been characterized thoroughly. Here, we have characterized a 93-amino acid MBD (MBD) of MucBP (LAF_0673) from Lactobacillus fermentum. Multiple sequence alignment of L. fermentum MBD exhibited ∼60% sequence homology with MBDs from other Lactobacillus species. Further, we cloned, expressed and purified MBD from Escherichia coli as N-terminal histidine-tagged protein (6X His-MBD). The purified MBD was able to bind to mucin and showed strong affinity towards the terminally expressed mucin glycans viz. N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), Galactose (Gal), and Sialic acid (N-acetylneuraminic acid; Neu5Ac). In silico experiments further confirmed the interaction between homology modeled MBD to mucin glycans through hydrogen-bonding with its surface amino acid residues Ser, Pro, Ile, Tyr and Ala. We also have demonstrated that MBD was able to inhibit the adhesion of enteric pathogens, including E. coli, Salmonella Paratyphi A, Shigella sonnei and Proteus vulgaris to mucin. Our results suggested that L. fermentum MBD is a functionally sufficient unit to act as an adhesin and to protect from invading enteric pathogens.</p>

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2018

Journal Article

V. S, A, S., Annapoorna, M., R, J., Subramania, I., V, N. Shantikuma, and R, J., “Injectable deferoxamine nanoparticles loaded chitosan-hyaluronic acid coacervate hydrogel for therapeutic angiogenesis.”, Colloids Surf B Biointerfaces, vol. 161, pp. 129-138, 2018.[Abstract]


<p>In this study, an injectable chitosan-hyaluronic acid (CS-HA) based hydrogel was designed incorporating pro-angiogenic molecule, deferoxamine loaded PLGA nanoparticles (DFO NPs), for enhancing angiogenesis. DFO-NPs were prepared by double emulsion solvent diffusion technique and characterized for their physicochemical properties. The DLS and SEM analysis showed an average particle size of 220±71nm with spherical morphology and the encapsulation efficiency was found to be 30±5%. An ECM mimicking chitosan-hyaluronic acid (CS-HA) coacervate hydrogel was prepared. Both free DFO and DFO NPs were entrapped into the prepared CS-HA composite hydrogel. The hydrogels were characterized by SEM, FTIR and Rheology. Addition of DFO NPs did not affect the injectablility and flowability of developed hydrogels. In vitro DFO release from the prepared composite hydrogels showed controlled release over a period of 10days. Both the hydrogel systems showed excellent cyto-compatability and good cell proliferation for rASCs as well as HUVECs. The DFO and DFO NPs loaded composite hydrogels revealed effective tube formation in comparison with control hydrogels without DFO and DFO NPs. The in vivo angiogenic evaluation of the free DFO and DFO NPs (0.025%w/w) loaded composite hydrogels were studied by injecting the developed hydrogel subcutaneously into mice for 2-4 weeks. The DFO NPs loaded composite hydrogel had enhanced neovascularization when compared to control gels. Thus, the developed DFO NPs loaded composite hydrogel could potentially be used for therapeutic angiogenesis.</p>

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2018

Journal Article

F. Basheer, Melge, A. R., Sasidharan, A., Nair, S. V., Manzoor, K., and C Mohan, G., “Computational simulations and experimental validation of structure- physicochemical properties of pristine and functionalized graphene: Implications for adverse effects on p53 mediated DNA damage response.”, Int J Biol Macromol, vol. 110, pp. 540-549, 2018.[Abstract]


<p>Recent reports indicated DNA damaging potential of few-layer graphene in human cell systems. Here, we used computational technique to understand the interaction of both pristine (pG) or carboxyl functionalized graphene (fG) of different sizes (1, 6, and 10nm) with an important DNA repair protein p53. The molecular docking study revealed strong interaction between pG and DNA binding domains (DBD) of p53 with binding free energies (BE) varying from -12.0 (1nm) to -34 (6nm)kcal/mol, while fG showed relatively less interaction with BE varying from -6.7 (1nm) to -11.1 (6nm)kcal/mol. Most importantly, pG or fG bound p53-DBDs could not bind to DNA. Further, microarray analysis of human primary endothelial cells revealed graphene intervention on DNA damage and its structure-properties effect using comet assay studies. Thus, computational and experimental results revealed the structure-physicochemical property dependent adverse effects of graphene in DNA repair protein p53.</p>

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2018

Journal Article

V. Aparna, Melge, A. Rohit, Rajan, V. K., Biswas, R., Jayakumar, R., and C Mohan, G., “Carboxymethylated ɩ-carrageenan conjugated amphotericin B loaded gelatin nanoparticles for treating intracellular Candida glabrata infections.”, Int J Biol Macromol, vol. 110, pp. 140-149, 2018.[Abstract]


<p>Intercellular Candida glabrata infections are difficult to treat due to poor penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B) into the macrophages where the pathogen inhabits is an effective solution. We are studying the macrophage targeting proficiency of ɩ-carrageenan for the delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A was the outcome of in silico inspections where the amino functionalized polymer having the best docking score with Amp B was selected. We prepared a sustained release formulation of amp B loaded carboxymethyl ɩ-carrageenan conjugated gelatin nanoparticles (CMC-Amp B-GNPs) with size 343±12nm and -25±5.3mV zeta potential. The formulations were found to be stable, biocompatible and non-haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced antifungal activity than bare Amp B and Amp B-GNPs.</p>

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2018

Journal Article

K. Parvathi, Krishnan, A. G., Anitha, A., Jayakumar, R., and Nair, M. B., “Poly(L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro.”, Int J Biol Macromol, vol. 110, pp. 514-521, 2018.[Abstract]


<p>Cissus quadrangularis (CQ) is known as "bone setter" in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications.</p>

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2018

Journal Article

G. Raju, Katiyar, N., Vadukumpully, S., and Shankarappa, S. A., “Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin.”, J Dermatol Sci, vol. 89, no. 2, pp. 146-154, 2018.[Abstract]


<p><b>BACKGROUND: </b>Transdermal particulate penetration across thick-skin, such as that of palms and sole, is particularly important for drug delivery for disorders such as small fiber neuropathies. Nanoparticle-based drug delivery across skin is believed to have much translational applications, but their penetration especially through thick-skin, is not clear.</p><p><b>OBJECTIVE: </b>This study specifically investigates the effectiveness of gold nanoparticles (AuNPs) for thick-skin penetration, especially across the stratum corneum (SC) as a function of particle size.</p><p><b>METHODS: </b>The thick-skinned hind-paw of rat was used to characterize depth and distribution of AuNPs of varying sizes, namely, 22±3, 105±11, and 186±20nm. Epidermal penetration of AuNPs was characterized both, in harvested skin from the hind-paw using a diffusion chamber, as well as in vivo.</p><p><b>RESULTS: </b>Harvested skin segments exposed to 22nm AuNPs for only 3h demonstrated higher penetration (p<0.05) as compared to the 105 and 186nm particles. In animal studies, hind-paw skin of adult rats exposed to AuNPs solution for the same time, demonstrated nanoparticles in blood on the 4th day, and histological analysis revealed AuNPs in epidermal layers just below the SC, with no apparent tissue response.</p><p><b>CONCLUSION: </b>We conclude that the thick-skin allows nanoparticle penetration and acts as a depot for release of AuNPs into circulation long after the initial exposure has ceased.</p>

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2018

Journal Article

B. Gangaja, Nair, S. V., and Santhanagopalan, D., “Interface-engineered LiTiO-TiO dual-phase nanoparticles and CNT additive for supercapacitor-like high-power Li-ion battery applications.”, Nanotechnology, vol. 29, no. 9, p. 095402, 2018.[Abstract]


<p>The single-pot synthesis of dual-phase spinel-LiTiO and anatase-TiO (LTO-TiO) nanoparticles over all the phase fractions ranging from pure LTO to pure TiO is conducted. Carrying out the process over the complete range enabled the identification of a unique weight ratio of 85:15 (LTO:TiO), providing the best combination of capacity, rate capability and cycling stability. We show that for this composition dual-phase nanoparticles have a predominant interfacial orientation of (111)∣∣(004) , while it is (111)∣∣(101) for other compositions. This study therefore shows that the dual-phase interface with these specific orientations gives the best performance. The synergistic combination of dual-phase nanoparticles with multi-wall carbon nanotubes improves the performance further. This results in an electrode with supercapacitor-like rate capability delivering high discharge capacities of 174, 127, 119, 110, 101 and 91 mAh g at specific currents of 2000, 6000, 12 000, 18 000, 24 000 and 30 000 mA g, respectively. A discharge capacity of 174 mAh g at a specific current of 2000 mA g with only 0.005% capacity loss per cycle over 3000 cycles is demonstrated. At current densities of 6000, 12 000 and 24 000 mA g, stable cycling is obtained for 1500 cycles. The present work enables nano-engineered interfaces in LTO-TiO dual-phase nanoparticles with an electrochemical performance that is better than its individual components, opening up the potential for high-power Li-ion battery applications.</p>

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2018

Journal Article

S. Deepthi, M Sundaram, N., Vijayan, P., Nair, S. V., and Jayakumar, R., “Engineering poly(hydroxy butyrate-co-hydroxy valerate) based vascular scaffolds to mimic native artery.”, Int J Biol Macromol, vol. 109, pp. 85-98, 2018.[Abstract]


<p>Electrospun tri-layered fibrous scaffold incorporating VEGF and Platelet Factor Concentrate (PFC) in multiple layers having different layer architectures was designed to mimic native artery. The scaffold consisted of longitudinally aligned poly(hydroxy butyrate-co-hydroxy valerate) (PHBV) and poly(vinyl alcohol) (PVA) nanofibers (inner layer), radially aligned PHBV-elastin nanofibers (middle layer) to provide the bi-directional alignment and combination of longitudinally aligned PHBV-elastin and random PHBV/PVA multiscale fibers (peripheral layer). Tubular constructs of diameter <6 mm were developed. The developed electrospun fibers were characterised by Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy and Tensile tests. Further the burst strength, compliance and stiffness index of tri-layered tubular scaffold was evaluated. SEM images of fibrous layers showed the typical longitudinal and radial alignment of fibers in the tubular construct. SEM images showed that the prepared PHBV nanofibers were in the range of 500-800 nm and PHBV microfibers were of 1-2 μm in diameter in the tri-layered electrospun membrane. PVA nanofibers were of size 200-250 nm. The tensile strength, percentage compliance and stiffness index of tri-layered membrane was in accordance with that of native small blood vessels. The developed tri-layered membrane was blood compatible, with hemolysis degree 0.85 ± 0.21% and did not activate platelets. Controlled release of VEGF and PFC was observed from the scaffold. The biocompatibility of the tri-layered scaffold was evaluated using HUVECs, SMCs and MSCs and SMCs infiltration from the outer layer was also evaluated. Specific protein expression for the HUVECs and SMCs was evaluated by flow cytometry and immunocytochemistry. HUVECs and SMCs exhibited good elongation and alignment along the direction of fibers and was found to maintain its CD31, VE-Cadherin and αSMA expression respectively. The results highlight the importance of bi-directional fiber alignment on the tri-layered electrospun scaffold as a suitable architectural prototype for vascular scaffolds to mimic the native arteries.</p>

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2018

Journal Article

M. Kumaran Sa Kumar, Nair, S., Mony, U., Kalingavarman, S., Venkat, R., Sivanarayanan, T. Balakrishn, Unni, A. Kodakara K., Rajeshkannan, R., Anandakuttan, A., Radhakrishnan, S., and Menon, K. N., “Significance of elevated Prohibitin 1 levels in Multiple Sclerosis patients lymphocytes towards the assessment of subclinical disease activity and its role in the central nervous system pathology of disease.”, Int J Biol Macromol, vol. 110, pp. 573-581, 2018.[Abstract]


<p>Multiple Sclerosis (MS) is an autoimmune-neurodegenerative disorder managed therapeutically by modulating lymphocytes activity which has potential in disease management. Prohibitin 1(PHB) that controls the reactive oxygen species (ROS) and present on the activated lymphocytes have significance in the therapy of MS as esters of fumaric acid that regulates ROS is in phase II/III clinical trials. Thus, we evaluated the expression levels of PHB1 in experimental autoimmune encephalomyelitis (EAE), the animal model of MS and on MS patient's lymphocytes. PHB levels in brain tissue of EAE animals were determined by immunoblotting and on blood lymphocytes from MS relapse, Remission, Optic Neuritis, Neurological controls and Healthy volunteers by FACS using anti-PHB and anti-CD45 antibodies. We observed significant elevation of PHB in EAE brains (91.0 ± 17.59%) vs controls (29.8 ± 12.9%) (p = 0.01) and on lymphocytes of MS patients in acute (73.5 ± 11.20%) or relapsing (69.3 ± 17.33%) phase compared to remission (45.9 ± 8.08%) [p = 0.034 acute vs remission; p = 0.004 relapse vs remission]. Up regulation of PHB in relapsing vs remission MS patients imply the potential use of PHB to clinically evaluate subclinical disease status towards prognosis of an oncoming relapse. Elevated PHB levels in EAE brains signify the role of PHB in regulating ROS and implies PHB's role in oxidative stress.</p>

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2018

Journal Article

J. Anjana, Mohandas, A., Seethalakshmy, S., Suresh, M. K., Menon, R., Biswas, R., and Jayakumar, R., “Bi-layered nanocomposite bandages for controlling microbial infections and overproduction of matrix metalloproteinase activity.”, Int J Biol Macromol, vol. 110, pp. 124-132, 2018.[Abstract]


<p>Chronic diabetic wounds is characterised by increased microbial contamination and overproduction of matrix metalloproteases that would degrade the extracellular matrix. A bi-layer bandage was developed, that promotes the inhibition of microbial infections and matrix metalloprotease (MMPs) activity. Bi-layer bandage containing benzalkonium chloride loaded gelatin nanoparticles (BZK GNPs) in chitosan-Hyaluronic acid (HA) as a bottom layer and sodium alendronate containing chitosan as top layer was developed. We hypothesized that the chitosan-gelatin top layer with sodium alendronate could inhibit the MMPs activity, whereas the chitosan-HA bottom layer with BZK GNPs (240±66nm) would enable the elimination of microbes. The porosity, swelling and degradation nature of the prepared Bi-layered bandage was studied. The bottom layer could degrade within 4days whereas the top layer remained upto 7days. The antimicrobial activity of the BZK NPs loaded bandage was determined using normal and clinical strains. Gelatin zymography shows that the proteolytic activity of MMP was inhibited by the bandage.</p>

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2018

Journal Article

T. S. Saranya, Rajan, V. K., Biswas, R., Jayakumar, R., and Sathianarayanan, S., “Synthesis, characterisation and biomedical applications of curcumin conjugated chitosan microspheres.”, Int J Biol Macromol, vol. 110, pp. 227-233, 2018.[Abstract]


<p>Curcumin is a diaryl heptanoid of curcuminoids class obtained from Curcuma longa. It possesses various biological activities like anti-inflammatory, hypoglycemic, antioxidant, wound-healing, and antimicrobial activities. Chitosan is a biocompatible, biodegradable and non-toxic natural polymer which enhances the adhesive property of the skin. Chemical conjugation will leads to sustained release action and to enhance the bioavailability. This study aims to synthesis and characterize biocompatible curcumin conjugated chitosan microspheres for bio-medical applications. The Schiff base reaction was carried out for the preparation of curcumin conjugated chitosan by microwave method and it was characterised using FTIR and NMR. Curcumin conjugated chitosan microspheres (CCCMs) were prepared by wet milling solvent evaporation method. SEM analysis showed these CCCMs were 2-5μm spherical particles. The antibacterial activities of the prepared CCCMs were studied against Staphylococcus aureus and Escherichia coli, the zone of inhibition was 28mm and 23mm respectively. Antioxidant activity of the prepared CCCMs was also studied by DPPH and HO method it showed IC esteem value of 216μg/ml and 228μg/ml, and anti-inflammatory activity results showed that CCCMs having IC value of 45μg/ml. The results conclude that the CCCMs having a good antibacterial, antioxidant and anti-inflammatory activities. This, the prepared CCCMs have potential application in preventing skin infections.</p>

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2018

Journal Article

S. Kuttappan, Anitha, A., Minsha Mallika Gopi, Menon, P. M., Sivanarayanan, T. B., Dr. Lakshmi Sumitra, and Dr. Manitha B. Nair, “BMP2 Expressing Genetically Engineered Mesenchymal Stem Cells on Composite Fibrous Scaffolds for Enhanced bone Regeneration in Segmental Defects”, Materials Science and Engineering: C, vol. 85, pp. 239 - 248, 2018.[Abstract]


The treatment of critical sized bone defect remains a significant challenge in orthopedics. The objective of the study is to evaluate the effect of the combination of bone morphogenetic protein 2 (BMP2) expressing genetically engineered mesenchymal stem cells (MSCs) [MSCs engineered using a multimam vector, pAceMam1, an emerging gene delivery vector] and an osteoconductive scaffold [silica coated nanohydroxyapatite-gelatin reinforced with fibers] in enhancing bone regeneration in critical sized segmental defects. The scaffold with transfected MSCs showed significantly higher viability, proliferation and osteogenic differentiation in vitro. Further, this group augmented union and new bone formation in critical sized rat femoral segmental defect at 12 weeks when compared to control groups (scaffold with MSCs and scaffold alone). These data demonstrated that the MSCs engineered for transient expression of BMP2 can improve the repair of segmental defects, which paves an avenue for using pAceMam1 as a vector for bone tissue regeneration.

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2018

Journal Article

S. Vignesh, Gopalakrishnan, A., Poorna, M. R., Shantikumar V Nair, Dr. Jayakumar Rangasamy, and Dr. Ullas Mony, “Fabrication of Micropatterned Alginate-gelatin and K-carrageenan Hydrogels of Defined Shapes using Simple Wax Mould Method as a Platform for Stem Cell/induced Pluripotent Stem Cells (iPSC) Culture”, International Journal of Biological Macromolecules, 2018.[Abstract]


Micropatterning techniques involve soft lithography, which is laborious, expensive and restricted to a narrow spectrum of biomaterials. In this work we report, first time employment of patterned wax moulds for generation of micropatterned alginate-gelatin and κ-carrageenan (κ-CRG) hydrogel systems by a novel, simple and cost effective method. We generated and characterized uniform and reproducible micropatterned hydrogels of varying sizes and shapes such as square projections, square grooves, and circular grids and crisscrossed hillocks. The rheological analysis showed that κ-carrageenan hydrogels had higher gel strength when compared to alginate-gelatin hydrogels. Human Mesenchymal stem cells (hMSCs) and Human Induced Pluripotent Stem Cells (hiPSCs) were found to be cytocompatible with these hydrogels. This micropatterned hydrogel system may have potential application in tissue engineering and also in understanding the basic biology behind the stem cell/iPSC fate.

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2018

Journal Article

V. Aparna, Shiva, M., Biswas, R., and Jayakumar, R., “Biological macromolecules based targeted nanodrug delivery systems for the treatment of intracellular infections.”, Int J Biol Macromol, vol. 110, pp. 2-6, 2018.[Abstract]


<p>Intracellular infections are tricky to treat, the reason being the poor penetration of antibiotics/antimycotics into the microbial niche (host cell). Macrophages are primary targets of facultative and obligate intracellular bacteria/fungi to be abused as host cells. The need for drugs with better intracellular penetration led to the development of endocytosable drug carriers, which can cross the cell membrane of the host cells (macrophages) by imitating the entry path of the pathogens. Therefore, the drugs can be targeted to macrophages ensuring enhanced therapeutic effect. This review discusses the exploitation of various nanocarriers for targeted delivery of drugs to the macrophages in the last two decades.</p>

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2018

Journal Article

R. Panonnummal, Jayakumar, R., Anjaneyan, G., and Sabitha, M., “In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.”, Int J Biol Macromol, vol. 110, pp. 259-268, 2018.[Abstract]


<p>The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis.</p>

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2018

Journal Article

S. Chandrashekaran, Karthikeyan, S., Balakrishnan, A., Nair, S., Kumar, M. Kumaran Sa, Vattathara, J. Jose, and Menon, K. N., “Expression and Purification of Quinine Dihydro Pteridine Reductase from astrocytes and its significance in the astrocyte pathology.”, Int J Biol Macromol, vol. 110, pp. 567-572, 2018.[Abstract]


<p>Quinine dihydropteridinereductase (QDPR) is involved in the synthesis of tetradihydrobiopteridine (BH4) that serve as cofactor for many aromatic hydroxylases including induced nitric oxide synthase (NOS) leading to NO production. Increased activity of QDPR has been associated with decrease levels of TGF-β, a cytokine that regulates the immune response and that elevated levels of NO has been associated with neurodegenerative diseases. Thus, expression of QDPR in astrocytes is essential to study the pathological changes observed in many neurodegenerative disorders. We have expressed QDPR in astrocytes and generated stably expressing clones that overexpresses QDPR. We further verified the specificity of QDPR expression using immunofluorescence and immunoblotting. To further confirm, we purified QDPR using Ni-NTA column and subjected the purified fraction to immunoblotting using anti-QDPR antibody and identified two major protein products of QDPR resolving at 25 and 17 kDa as reported in the literature. In order to further assess the significance of QDPR expression, we verified the expression of iNOS in QDPR over expressing cells. We show for the first time statistically significant up regulation of iNOS in QDPR overexpressing astrocytes. Increased expression of iNOS associated with astrocyte pathology seen in many neurodegenerative disorders may have implications in autoimmune neurodegenerative disorders.</p>

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2018

Journal Article

M. Sandhya, V, A., K, S. Maneesha, Raja, B., R, J., and S, S., “Amphotericin B loaded sulfonated chitosan nanoparticles for targeting macrophages to treat intracellular Candida glabrata infections.”, Int J Biol Macromol, vol. 110, pp. 133-139, 2018.[Abstract]


<p>The current study assesses the potential of functionalised chitosan nanoparticles (CNPs) for proficient macrophage delivery of amphotericin B (AmpB) for the management of Candida glabrata fungemia. Chitosan was functionalised by the method of sulfation by using chlorosulfonic acid and the developed compound was confirmed by FTIR, H NMR and degree of sulfation and CHNS analysis. Amphotericin B encapsulated sulfated chitosan (AmpB-SCNPs), when characterized showed a hydrodynamic diameter of 310 ± 14 nm and zeta potential of 41.5 ± 2 mV. The safety of AmpB-SCNPs was established by the alamar cytotoxicity assay in nanoparticle treated macrophages following 24 h incubation. The AmpB-SCNPs showed a significant increase in the reduction of C. glabrata in comparison with the bare AmpB and AmpB-CNPs (55.2 and 42.7 vs 11.12 cfu/ml) indicating that AmpB-SCNPs could be a promising carrier for specific delivery of AmpB to macrophages for effective treatment of Candida glabrata fungemia.</p>

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2018

Journal Article

S. Padmakumar, Parayath, N., Leslie, F., Nair, S. V., Menon, D., and Amiji, M. M., “Intraperitoneal chemotherapy for ovarian cancer using sustained-release implantable devices.”, Expert Opin Drug Deliv, vol. 15, no. 5, pp. 481-494, 2018.[Abstract]


<p><b>INTRODUCTION: </b>Epithelial ovarian cancer (EOC) remains to be the most lethal of all gynecological malignancies mainly due to its asymptomatic nature. The late stages are manifested with predominant metastases confined to the peritoneal cavity. Although there has been a substantial progress in the treatment avenue with different therapeutic interventions, the overall survival rate of patients remain poor due to relapse and drug resistance. Areas covered: The pharmacokinetic advantages offered by intraperitoneal (IP) chemotherapy due to peritoneal-plasma barrier can be potentially exploited for EOC relapse treatment. The ability to retain high concentrations of chemo-drugs with high AUC peritoneum/plasma for prolonged durations in the peritoneal cavity can be utilized effectively through the clinical adoption of drug delivery systems (DDSs) which obviates the need for indwelling catheters. The metronomic dosing strategy could enhance anti-tumor efficacy with a continuous, low dose of chemo-drugs providing minimal systemic toxicity. Expert opinion: The development of a feasible, non-catheter based, IP DDS, retaining the peritoneal-drug levels, with less systemic levels could offer significant survival advantages as a patient-compliant therapeutic strategy. Suturable-implantable devices based on metronomic dosing, eluting drug in a sustained manner at low doses, could be implanted surgically post-debulking for treatment of refractory EOC patients.</p>

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2018

Journal Article

S. Vignesh, Gopalakrishnan, A., R, P. M., Nair, S. V., Jayakumar, R., and Mony, U., “Fabrication of micropatterned alginate-gelatin and k-carrageenan hydrogels of defined shapes using simple wax mould method as a platform for stem cell/induced Pluripotent Stem Cells (iPSC) culture.”, Int J Biol Macromol, vol. 112, pp. 737-744, 2018.[Abstract]


<p>Micropatterning techniques involve soft lithography, which is laborious, expensive and restricted to a narrow spectrum of biomaterials. In this work we report, first time employment of patterned wax moulds for generation of micropatterned alginate-gelatin and κ-carrageenan (κ-CRG) hydrogel systems by a novel, simple and cost effective method. We generated and characterized uniform and reproducible micropatterned hydrogels of varying sizes and shapes such as square projections, square grooves, and circular grids and crisscrossed hillocks. The rheological analysis showed that κ-carrageenan hydrogels had higher gel strength when compared to alginate-gelatin hydrogels. Human Mesenchymal stem cells (hMSCs) and Human Induced Pluripotent Stem Cells (hiPSCs) were found to be cytocompatible with these hydrogels. This micropatterned hydrogel system may have potential application in tissue engineering and also in understanding the basic biology behind the stem cell/iPSC fate.</p>

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2018

Journal Article

A. Ashok, Vijayaraghavan, S. N., Unni, G. E., Nair, S. V., and Shanmugam, M., “On the physics of dispersive electron transport characteristics in SnO nanoparticle-based dye sensitized solar cells.”, Nanotechnology, vol. 29, no. 17, p. 175401, 2018.[Abstract]


The present study elucidates dispersive electron transport mediated by surface states in tin oxide (SnO) nanoparticle-based dye sensitized solar cells (DSSCs). Transmission electron microscopic studies on SnO show a distribution of ∼10 nm particles exhibiting (111) crystal planes with inter-planar spacing of 0.28 nm. The dispersive transport, experienced by photo-generated charge carriers in the bulk of SnO, is observed to be imposed by trapping and de-trapping processes via SnO surface states present close to the band edge. The DSSC exhibits 50% difference in performance observed between the forward (4%) and reverse (6%) scans due to the dispersive transport characteristics of the charge carriers in the bulk of the SnO. The photo-generated charge carriers are captured and released by the SnO surface states that are close to the conduction band-edge resulting in a very significant variation; this is confirmed by the hysteresis observed in the forward and reverse scan current-voltage measurements under AM1.5 illumination. The hysteresis behavior assures that the charge carriers are accumulated in the bulk of electron acceptor due to the trapping, and released by de-trapping mediated by surface states observed during the forward and reverse scan measurements.

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2018

Journal Article

S. Nithya, Nimal, T. R., Baranwal, G., Suresh, M. K., P, A. C., V Kumar, A., C Mohan, G., Jayakumar, R., and Biswas, R., “Preparation, characterization and efficacy of lysostaphin-chitosan gel against Staphylococcus aureus.”, Int J Biol Macromol, vol. 110, pp. 157-166, 2018.[Abstract]


<p>Lysostaphin (LST) is a bacteriocin that cleaves within the pentaglycine cross bridge of Staphylococcus aureus peptidoglycan. Previous studies have reported the high efficiency of LST even against multi drug resistant S. aureus including methicillin resistant S. aureus (MRSA). In this study, we have developed a new chitosan based hydrogel formulation of LST to exploit its anti-staphylococcal activity. The atomic interactions of LST with chitosan were studied by molecular docking studies. The rheology and the antibacterial properties of the developed LSTC gel were evaluated. The developed LST containing chitosan hydrogel (LSTC gel) was flexible, flows smoothly and remains stable at physiological temperature. The in vitro studies by agar well diffusion and ex vivo studies in porcine skin model exhibited a reduction in S. aureus survival by ∼3 LogCFU/mL in the presence of LSTC gel. The cytocompatibility of the gel was tested in vitro using macrophage RAW 264.7 cell line and in vivo in Drosophila melanogaster. A gradual disruption of S. aureus biofilms with the increase of LST concentrations in the LSTC gel was observed which was confirmed by SEM analysis. We conclude that LSTC gel could be highly effectual and advantageous over antibiotics in treating staphylococcal-topical and biofilm infections.</p>

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2018

Journal Article

V. Soman Pillai, Kundargi, R. R., Edathadathil, F., Nair, S., Thilak, J., Mathew, R. Anney, Xavier, T., Shenoy, P., and Menon, K. N., “Identification of prolargin expression in articular cartilage and its significance in rheumatoid arthritis pathology.”, Int J Biol Macromol, vol. 110, pp. 558-566, 2018.[Abstract]


<p>Qualitative 2D gel-electrophoresis (2DE) protein profiling for osteoarthritis (OA) and rheumatoid arthritis (RA) is challenging because of selective protein loss due to discrepancies in protein precipitation methodologies. Thus, we aimed at developing qualitative protein representation from OA/RA articular cartilage without protein precipitation towards identification of clinically relevant proteins. Chondroitinase digested human articular cartilages from RA patients were subjected to protein extraction using guanidinium hydrochloride (GuHCl) or 8 M urea with 10 or 2% ASB-14-4 or 0.45 M urea with 2% ASB-14-4 with cetylpyridinium chloride (CPC). The GuHCl extract is further protein precipitated with acetone or ammonium acetate-methanol or centricon-fractionated using 100 kDa cut filters and protein precipitated using ethanol. Processed extracts were subjected to 2DE to identify protein profiles. Poor proteins representations were observed in 2D gels with protein precipitated samples compared to qualitative protein representations seen in 2D gels of 0.45 M urea and 2%ASB-14-4 extraction procedure reproducibly. The strategy circumventing protein precipitation generated qualitative 2D gels. RA vs OA gel comparison showed elevated prolargin levels in RA with biglycan levels remaining unaltered. Up regulation of prolargin in RA suggests the likelihood of an adaptive mechanism to control the increased osteoclastogenesis in RA and may have therapeutic value in controlling the disease.</p>

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2018

Journal Article

C. Porayath, M. K. Suresh, Dr. Raja Biswas, Dr. Bipin G. Nair, Dr. Nandita Mishra, and Dr. Sanjay Pal, “Autolysin mediated adherence of Staphylococcus aureus with Fibronectin, Gelatin and Heparin.”, International Journal of Biological Macromolecules, vol. 110, pp. 179-184, 2018.[Abstract]


Major autolysin (Atl) of Staphylococcus aureusis a cell surface associated peptidoglycan hydrolase with amidase and glucosaminidase domains. Atl enzymes (amidase and glucosaminidase) are known to participate in biofilm formation and also can bind with host matrices. Earlier studies demonstrated the binding of Atlwithfibronectin, thrombospondin 1, vitronectin and heat shock cognate protein Hsc70. Here, we have shown, Atl mediates attachment of S.aureus to heparin and gelatine as well. The atl mutant strain demonstrated around 2.5 fold decreased adherence with fibronectin, gelatin and heparin coated microtiter plates. The microscopic studies confirmed the reduced binding of atl mutant with them compared to its parental wild type and complemented mutant strains. Amidase and glucosaminidase were expressed as N-terminal histidine tagged proteins from Escherichia coli, purified and refolded. We found refolded amidase bind with fibronectin, gelatin and heparin; whereas refolded glucosaminidase binds with only fibronectin and heparin but not gelatin. These results reemphasize Atl as one of the crucial proteins from Staphylococcus that facilitate their binding with multiple host cellular components during colonization and infection.

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2018

Journal Article

V. Aparna, Shiva, M., Biswas, R., and Jayakumar, R., “Biological macromolecules based targeted nanodrug delivery systems for the treatment of intracellular infections”, International Journal of Biological Macromolecules, vol. 110, pp. 2-6, 2018.[Abstract]


Intracellular infections are tricky to treat, the reason being the poor penetration of antibiotics/antimycotics into the microbial niche (host cell). Macrophages are primary targets of facultative and obligate intracellular bacteria/fungi to be abused as host cells. The need for drugs with better intracellular penetration led to the development of endocytosable drug carriers, which can cross the cell membrane of the host cells (macrophages) by imitating the entry path of the pathogens. Therefore, the drugs can be targeted to macrophages ensuring enhanced therapeutic effect. This review discusses the exploitation of various nanocarriers for targeted delivery of drugs to the macrophages in the last two decades. © 2018 Elsevier B.V.

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2018

Journal Article

V. S. Pillai, Kundargi, R. R., Edathadathil, F., Nair, S., Thilak, J., Mathew, R. A., Xavier, T., Shenoy, P., and Krishnakumar N. Menon, “Identification of Prolargin Expression in Articular Cartilage and its Significance in Rheumatoid Arthritis Pathology”, International Journal of Biological Macromolecules, 2018.[Abstract]


Qualitative 2D gel-electrophoresis (2DE) protein profiling for osteoarthritis (OA) and rheumatoid arthritis (RA) is challenging because of selective protein loss due to discrepancies in protein precipitation methodologies. Thus, we aimed at developing qualitative proteinrepresentation from OA/RA articular cartilage without protein precipitation towards identification of clinically relevant proteins. Chondroitinase digested human articular cartilages from RA patients were subjected to protein extraction using guanidinium hydrochloride (GuHCl) or 8 M urea with 10 or 2% ASB-14-4 or 0.45 M urea with 2% ASB-14-4 with cetylpyridinium chloride (CPC). The GuHCl extract is further protein precipitated with acetone or ammonium acetate-methanol or centricon-fractionated using 100 kDa cut filters and protein precipitated using ethanol. Processed extracts were subjected to 2DE to identify protein profiles. Poor proteins representations were observed in 2D gels with protein precipitated samples compared to qualitative protein representations seen in 2D gels of 0.45 M urea and 2%ASB-14-4 extraction procedure reproducibly. The strategy circumventing protein precipitation generated qualitative 2D gels. RA vs OA gel comparison showed elevated prolargin levels in RA with biglycan levels remaining unaltered. Up regulation of prolargin in RA suggests the likelihood of an adaptive mechanism to control the increased osteoclastogenesis in RA and may have therapeutic value in controlling the disease.

More »»

2018

Journal Article

S. Nithya, Nimal, T. R., Baranwal, G., Suresh, M. K., C.P., A., V. Kumar, A., Dr. Gopi Mohan C., Jayakumar, R., and Dr. Raja Biswas, “Preparation, Characterization and Efficacy of Lysostaphin-chitosan Gel Against Staphylococcus Aureus”, International Journal of Biological Macromolecules, 2018.[Abstract]


Lysostaphin (LST) is a bacteriocin that cleaves within the pentaglycine cross bridge of Staphylococcus aureus peptidoglycan. Previous studies have reported the high efficiency of LST even against multi drug resistant S. aureus including methicillin resistant S. aureus (MRSA). In this study, we have developed a new chitosan based hydrogel formulation of LST to exploit its anti-staphylococcal activity. The atomic interactions of LST with chitosan were studied by molecular docking studies. The rheology and the antibacterial properties of the developed LSTC gel were evaluated. The developed LST containing chitosan hydrogel (LSTC gel) was flexible, flows smoothly and remains stable at physiological temperature. The in vitro studies by agar well diffusion and ex vivo studies in porcine skin model exhibited a reduction in S. aureus survival by 3 Log10CFU/mL in the presence of LSTC gel. The cytocompatibility of the gel was tested in vitro using macrophage RAW 264.7 cell line and in vivo in Drosophila melanogaster. A gradual disruption of S. aureus biofilms with the increase of LST concentrations in the LSTC gel was observed which was confirmed by SEM analysis. We conclude that LSTC gel could be highly effectual and advantageous over antibiotics in treating staphylococcal-topical and biofilm infections.

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2018

Journal Article

A. R. Melge, Prakash, O., S, S., Dr. Raja Biswas, Biswas, L., and Dr. Gopi Mohan C., “Structure-Function Studies of Prothrombin Amrita, a Dysfunctional Prothrombin Characterized by Point Mutation at Arg553 → Gln”, International Journal of Biological Macromolecules, 2018.[Abstract]


A dysfunctional prothrombin gene characterized by novel point mutation at Arg553 to Gln residue in Deep vein thrombosis (DVT) patient which we designated as "Prothrombin Amrita" was previously reported from our lab. The mutation occurred at nucleotide 20030 in exon 14 and was confirmed by restriction enzyme digestion. Arg553 has been reported as one of the key residues for the binding of cofactor Na+ ion in the thrombin protein. Structural analysis revealed the molecular mechanism behind the coagulant form of thrombin due to point Arg553Gln mutation near the cofactor Na+ ion region. Molecular electrostatic potential maps and molecular dynamics (MD) simulation of the wild type and mutated thrombin showed the key role played by the Na+ ion for its coagulant mechanism by analysing the charge distribution and nature of the hydrogen bonding at the mutated region of interest. We observed maintenance of the fast or procoagulant form of dysfunctional prothrombin due to changes in the charge distribution by this mutation and thereby also keeping strong hydrogen bonding network revealed by MD simulation between prothrombin and Na+ ion. This molecular mechanism might be the main cause for DVT in patients with this dysfunctional prothrombin gene.

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2018

Journal Article

S. K. Vettath, Shivashankar, G., Krishnakumar N. Menon, and Dr. Lakshmi Sumitra, “Recombinant Expression of Extracellular Domain of Mutant Epidermal Growth Factor Receptor in Prokaryotic and Baculovirus Expression Systems”, International Journal of Biological Macromolecules, 2018.[Abstract]


Epidermal Growth Factor Receptor variant III (EGFRvIII) is a tumor specific antigen detected in various tumors including gliomas, breast cancer, lung cancer, head and neck squamous cell carcinoma (HNSCC). Screening of EGFRvIII targeting drug molecules can be accelerated by developing drug screening platforms using recombinantly expressed protein. Choice of expression system is one of the major factors deciding the success of recombinant expression of a protein. In our study, we have tried to express and purify the extracellular domain (ECD) of this highly unstable protein using bacterial and baculovirus expression systems to select the expression system suited for our purpose. Even though the protein was successfully expressed in prokaryotic system, purification could be done only under denaturing conditions. But in the baculovirus expression system, the protein was expressed in soluble form and could be purified under native conditions, with single step of purification. Based on our results, we conclude that insect cells are better choice over E. coli cells for expressing EGFRvIII ECD in soluble form. This study provides insights for other researchers involved in expression of similar unstable membrane proteins, on selecting the best expression system and challenges involved.

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2018

Journal Article

S. Chandrashekaran, Karthikeyan, S., Balakrishnan, A., Nair, S., Kumar, M. K. Satheesh, Vattathara, J. J., and Menon, K. N., “Expression and Purification of Quinine Dihydro Pteridine Reductase from astrocytes and its significance in the astrocyte pathology”, International Journal of Biological Macromolecules, 2018.[Abstract]


Quinine dihydropteridinereductase (QDPR) is involved in the synthesis of tetradihydrobiopteridine (BH4) that serve as cofactor for many aromatic hydroxylases including induced nitric oxide synthase (NOS) leading to NO production. Increased activity of QDPR has been associated with decrease levels of TGF-β, a cytokine that regulates the immune response and that elevated levels of NO has been associated with neurodegenerative diseases. Thus, expression of QDPR in astrocytes is essential to study the pathological changes observed in many neurodegenerative disorders. We have expressed QDPR in astrocytes and generated stably expressing clones that overexpresses QDPR. We further verified the specificity of QDPR expression using immunofluorescence and immunoblotting. To further confirm, we purified QDPR using Ni-NTA column and subjected the purified fraction to immunoblotting using anti-QDPR antibody and identified two major protein products of QDPR resolving at 25 and 17 kDa as reported in the literature. In order to further assess the significance of QDPR expression, we verified the expression of iNOS in QDPR over expressing cells. We show for the first time statistically significant up regulation of iNOS in QDPR overexpressing astrocytes. Increased expression of iNOS associated with astrocyte pathology seen in many neurodegenerative disorders may have implications in autoimmune neurodegenerative disorders. © 2018 Elsevier B.V.

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2018

Journal Article

J. Z. Lee, Wynn, T. A., Meng, Y. Shirley, and Santhanagopalan, D., “Focused Ion Beam Fabrication of LiPON-based Solid-state Lithium-ion Nanobatteries for In Situ Testing.”, J Vis Exp, no. 133, 2018.[Abstract]


<p>Solid-state electrolytes are a promising replacement for current organic liquid electrolytes, enabling higher energy densities and improved safety of lithium-ion (Li-ion) batteries. However, a number of setbacks prevent their integration into commercial devices. The main limiting factor is due to nanoscale phenomena occurring at the electrode/electrolyte interfaces, ultimately leading to degradation of battery operation. These key problems are highly challenging to observe and characterize as these batteries contain multiple buried interfaces. One approach for direct observation of interfacial phenomena in thin film batteries is through the fabrication of electrochemically active nanobatteries by a focused ion beam (FIB). As such, a reliable technique to fabricate nanobatteries was developed and demonstrated in recent work. Herein, a detailed protocol with a step-by-step process is presented to enable the reproduction of this nanobattery fabrication process. In particular, this technique was applied to a thin film battery consisting of LiCoO2/LiPON/a-Si, and has further been previously demonstrated by in situ cycling within a transmission electron microscope.</p>

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2018

Journal Article

S. Karumathil, Raveendran, N. T., Ganesh, D., Ns, S. Kumar, Nair, R. R., and Dirisala, V. R., “Evolution of Synonymous Codon Usage Bias in West African and Central African Strains of Monkeypox Virus.”, Evol Bioinform Online, vol. 14, p. 1176934318761368, 2018.[Abstract]


<p>The evolution of bias in synonymous codon usage in chosen monkeypox viral genomes and the factors influencing its diversification have not been reported so far. In this study, various trends associated with synonymous codon usage in chosen monkeypox viral genomes were investigated, and the results are reported. Identification of factors that influence codon usage in chosen monkeypox viral genomes was done using various codon usage indices, such as the relative synonymous codon usage, the effective number of codons, and the codon adaptation index. The Spearman rank correlation analysis and a correspondence analysis were used for correlating various factors with codon usage. The results revealed that mutational pressure due to compositional constraints, gene expression level, and selection at the codon level for utilization of putative optimal codons are major factors influencing synonymous codon usage bias in monkeypox viral genomes. A cluster analysis of relative synonymous codon usage values revealed a grouping of more virulent strains as one major cluster (Central African strains) and a grouping of less virulent strains (West African strains) as another major cluster, indicating a relationship between virulence and synonymous codon usage bias. This study concluded that a balance between the mutational pressure acting at the base composition level and the selection pressure acting at the amino acid level frames synonymous codon usage bias in the chosen monkeypox viruses. The natural selection from the host does not seem to have influenced the synonymous codon usage bias in the analyzed monkeypox viral genomes.</p>

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2018

Journal Article

S. Karuppath, Pillai, P., Nair, S. V., and Lakshmanan, V. - K., “Comparison and existence of nanotechnology in traditional alternative medicine: An onset to future medicine”, Nanoscience and Nanotechnology - Asia, vol. 8, pp. 13-25, 2018.[Abstract]


Introduciton: Alternative medicine, one of the oldest systems of medicine, has given great emphasis to the promotion of health. Formulations of alternative medicine consist of substances of herbal, minerals/metals and animal origin which have processed pharmaceutically to have therapeutic effects. These core concepts allow implementation of ways for not only personalized medicine and treatment but also personalized prevention. In the realm of medicine, Nanotechnology holds promises due to its novel drug formulation routes, site-specific action, better solubility, improved efficacy and reduced side effects. Conclusion: This review was undertaken to consolidate the evidence of such associations which exist between traditional medicine and the Nanotechnology concepts of modern medicine. Traditional medicine with new scientific advancements in medical science and diagnostics along with nanotechnology will be greatly beneficial. This unique combination ushers a new era of affordable, safe and effective medicinal system. © 2018 Bentham Science Publishers.

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2018

Journal Article

Dr. Jayakumar Rangasamy, “SI: Biological Macromolecules for Delivery, Imaging & Therapy (BMDIT-2018)”, International Journal of Biological Macromolecules, vol. 110, p. 1, 2018.

2018

Journal Article

S. S. Jayasree, Nair, S., and Dr. Dhamodaran Santhanagopalan, “Ultrathin TiO2 Coating on LiCoO2 for Improved Electrochemical Performance as Li–Ion Battery Cathode”, ChemistrySelect, vol. 3, pp. 2763-2766, 2018.[Abstract]


Surface modification of LiCoO2 (LCO) gained much attention as it could play a prominent role in improving electrochemical performance and structural stability. Herein, we report an ultra-thin TiO2 coating on LiCoO2 (LCO-TiO2) as a potential candidate to overcome the electrochemical, structural instability and interface issues of the bare-LCO. The structural properties as well as electrochemical performances of bare-LCO and LCO-TiO2 were investigated by X-Ray diffraction, Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), Galvanostatic charge-discharge and electrochemical impedance spectroscopy (EIS). At the end of 100 cycles, 1C rate capacity retention was about 50% and 90% for bare-LCO and LCO-TiO2 respectively. Rate studies showed that the bare LCO exhibited a specific capacity of ∼120 mAh/g and only 16 mAh/g at 1C and 60 discharge rates respectively whereas, the TiO2 coated LCO showed a capacity of ∼132 mAh/g and nearly 98 mAh/g at 1C and 60C discharge rates respectively. The implementation of TiO2 coating over LiCoO2 enhanced the electrochemical performance, cell stability as well as efficiency. © 2018 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

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2018

Journal Article

S. Suresh, Unni, G. E., Satyanarayana, M., A Nair, S., and Pillai, V. P. Mahadeva, “Silver nanoparticles-incorporated NbO surface passivation layer for efficiency enhancement in dye-sensitized solar cells.”, J Colloid Interface Sci, vol. 524, pp. 236-244, 2018.[Abstract]


Guiding and capturing photons at the nanoscale by means of metal nanoparticles and interfacial engineering for preventing back-electron transfer are well documented techniques for performance enhancement in excitonic solar cells. Drifting from the conventional route, we propose a simple one-step process to integrate both metal nanoparticles and surface passivation layer in the porous photoanode matrix of a dye-sensitized solar cell. Silver nanoparticles and NbO surface passivation layer are simultaneously deposited on the surface of a highly porous nanocrystalline TiO photoanode, facilitating an absorption enhancement in the 465 nm and 570 nm wavelength region and a reduction in back-electron transfer in the fabricated dye-sensitized solar cells together. The TiO photoanodes were prepared by spray pyrolysis deposition method from a colloidal solution of TiO nanoparticles. An impressive 43% enhancement in device performance was accomplished in photoanodes having an Ag-incorporated NbO passivation layer as against a cell without Ag nanoparticles. By introducing this idea, we were able to record two benefits - the metal nanoparticles function as the absorption enhancement agent, and the NbO layer as surface passivation for TiO nanoparticles and as an energy barrier layer for preventing back-electron transfer - in a single step.

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2018

Journal Article

R. Jayakumar, “SI: Biological macromolecules for delivery, imaging & therapy (BMDIT-2018).”, Int J Biol Macromol, vol. 110, p. 1, 2018.

2018

Journal Article

A. Jose, Surendran, M., Fazal, S., Prasanth, B. - P., and Menon, D., “Multifunctional fluorescent iron quantum clusters for non-invasive radiofrequency ablationof cancer cells.”, Colloids Surf B Biointerfaces, vol. 165, pp. 371-380, 2018.[Abstract]


<p>This work reports the potential of iron quantum clusters (FeQCs) as a hyperthermia agent for cancer, by testing its in-vitro response to shortwave (MHz range), radiofrequency (RF) waves non-invasively. Stable, fluorescent FeQCs of size ∼1 nm prepared by facile aqueous chemistry from endogenous protein haemoglobin were found to give a high thermal response, with a ΔT ∼50 °C at concentrationsas low as165 μg/mL. The as-prepared nanoclusters purified by lyophilization as well as dialysis showed a concentration, power and time-dependent RF response, with the lyophilized FeQCs exhibiting pronounced heating effects. FeQCs were found to be cytocompatible to NIH-3T3 fibroblast and 4T1 cancer cells treated at concentrations upto 1000 μg/mL for 24 h. Upon incubation with FeQCs and exposure to RF waves, significant cancer cell death was observed which proves its therapeutic ability. The fluorescent ability of the clusters could additionally be utilized for imaging cancer cells upon excitation at ∼450 nm. Further, to demonstrate the feasibility of imparting additional functionality such as drug/biomolecule/dye loading to FeQCs, they were self assembled with cationic polymers to form nanoparticles. Self assembly did not alter the RF heating potential of FeQCs and additionally enhanced its fluorescence. The multifunctional fluorescent FeQCs therefore show good promise as a novel therapeutic agent for RF hyperthermia and drug loading.</p>

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2018

Journal Article

J. Z. Lee, Wynn, T. A., Meng, Y. S., and Dr. Dhamodaran Santhanagopalan, “Focused ion beam fabrication of LiPON-based solid-state lithium-ion nanobatteries for in situ testing”, Journal of Visualized Experiments, vol. 2018, 2018.[Abstract]


Solid-state electrolytes are a promising replacement for current organic liquid electrolytes, enabling higher energy densities and improved safety of lithium-ion (Li-ion) batteries. However, a number of setbacks prevent their integration into commercial devices. The main limiting factor is due to nanoscale phenomena occurring at the electrode/electrolyte interfaces, ultimately leading to degradation of battery operation. These key problems are highly challenging to observe and characterize as these batteries contain multiple buried interfaces. One approach for direct observation of interfacial phenomena in thin film batteries is through the fabrication of electrochemically active nanobatteries by a focused ion beam (FIB). As such, a reliable technique to fabricate nanobatteries was developed and demonstrated in recent work. Herein, a detailed protocol with a step-by-step process is presented to enable the reproduction of this nanobattery fabrication process. In particular, this technique was applied to a thin film battery consisting of LiCoO2/LiPON/a-Si, and has further been previously demonstrated by in situ cycling within a transmission electron microscope. © 2018, Journal of Visualized Experiments.

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2018

Journal Article

K. T. Shalumon, Anjana, J., Dr. Ullas Mony, Dr. Jayakumar Rangasamy, and Chen, J. - P., “Process Study, Development and Degradation Behavior of Different Size Scale Electrospun Poly(caprolactone) and Poly(lactic acid) Fibers”, Journal of Polymer Research, vol. 25, 2018.[Abstract]


This study describes the preparation of electrospun poly(caprolactone) (PCL) and poly(lactic acid) (PLA) fibrous scaffolds with and without nano-hydroxyapatite (nHAp) having nanoscale, microscale and combined micro/nano (multiscale) architecture. Processing parameters such as polymer concentration, voltage, flow rate and solvent compositions were varied in wide range to display the effect of each one in determining the diameter and morphology of fibers. The effect of each regulating parameter on fiber morphology and diameter was evaluated and characterized using scanning electron microscope (SEM). Degradability of the selected fibrous scaffolds was verified by phosphate buffered saline immersion and its morphology was analyzed through SEM, after 5 and 12&nbsp;months. Quantitative measurement in degradation was further evaluated through pH analysis of the medium. Both studies revealed that PLA had faster degradation compared to PCL irrespective of the size scale nature of fibers. Structural stability evaluation of the degraded fibers in comparison with pristine fibers by thermogravimetric analysis further confirmed faster degradability of PLA compared to PCL fibers. The results indicate that PLA showed faster degradation than PCL irrespective of the size-scale nature of fibrous scaffolds, and therefore, could be applied in a variety of biomedical applications including tissue engineering. © 2018, Springer Science+Business Media B.V., part of Springer Nature

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2018

Journal Article

H. Menon, Gopakumar, G., Vijayaraghavan, S. N., Shantikumar V Nair, and Dr. Mariyappan Shanmugam, “2D Layered MoS2 Incorporated TiO2 Nanofiber Based Dye Sensitized Solar Cells”, ChemistrySelect , 2018.

2018

Journal Article

A. Ashok, Mathew, S. E., Shivaram, S. B., Dr. Sahadev Shankarappa, Shantikumar V. Nair, and Dr. Mariyappan Shanmugam, “Cost Effective Natural Photo-sensitizer from Upcycled Jackfruit Rags for Dye Sensitized Solar Cells”, Journal of Science: Advanced Materials and Devices, p. -, 2018.[Abstract]


Abstract Photo-sensitizers, usually organic dye molecules, are considered to be one of the most expensive components in dye sensitized solar cells (DSSCs). The present work demonstrates a cost effective and high throughput upcycling process on jackfruit rags to extract a natural photo-active dye and its application as a photo-sensitizing candidate on titanium dioxide (TiO2) in DSSCs. The jackfruit derived natural dye (JDND) exhibits a dominant photo-absorption in a spectral range of 350 nm-800 nm with an optical bandgap of ∼1.1 eV estimated from UV-Visible absorption spectroscopic studies. The \{JDND\} in \{DSSCs\} as a major photo-absorbing candidate exhibits a photo-conversion efficiency of ∼1.1 % with short circuit current density and open circuit voltage of 2.2 mA.cm-2 and 805 mV respectively. Further, the results show that concentration of \{JDND\} plays an influential role on photovoltaic performance of the \{DSSCs\} due to the significant change in photo-absorption, exciton generation and electron injection into TiO2. The simple, high throughput method used to obtain \{JDND\} and the resulting \{DSSC\} performance can be considered as potential merits establishing a cost effective excitonic photovoltaic technology.

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2018

Journal Article

A. Ashok, Gopakumar, G., Vijayaraghavan, S. N., Shantikumar V. Nair, and Dr. Mariyappan Shanmugam, “Understanding Hysteresis Behavior in SnO2 Nanofiber Based Dye Sensitized Solar Cell”, Journal of Photovoltaics , 2018.[Abstract]


Tin oxide (SnO2) nanofiber-based dye-sensitized solar cell (DSSC) exhibits an anomalous hysteresis effect on its current–voltage characteristics. While the one-dimensional nature of SnO2 nanofibers is considered facilitating effective charge transport in DSSCs, the surface states present in the SnO2 bandgap are observed to be playing an influential role in trapping and detrapping of charge carriers in the bulk as confirmed by electrochemical impedance spectroscopic studies. Forward and backward electrical bias sweeps identify the hysteresis effect in the performance of resulting DSSCs due to which 43% difference was observed in the photovoltaic performance. Charge carriers generated in the dye utilize the SnO2 nanofiber as a transport medium to reach electrode through energetically active SnO2 surface states which effectively trap and detrap the photogenerated charges during the transport resulting in the hysteresis effect. The observed hysteresis effect varies the maximum power density (PMAX) and fill factor (FF) of the resulting DSSC by 35% and 25%, respectively, between forward and backward scans. The significant change in PMAX and FF asserts that trapping and detrapping mediated charge transport process contributed to the variation in overall performance by 43%.

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2018

Journal Article

G. Gopakumar, Ashok, A., Vijayaraghavan, S. N., Shantikumar V. Nair, and Dr. Mariyappan Shanmugam, “MoO3 Surface Passivation on TiO2: An Efficient Approach to Minimize Loss in Fill Factor and Maximum Power of Dye Sensitized Solar Cell”, Applied Surface Science, vol. 447, pp. 554 - 560, 2018.[Abstract]


The present study demonstrates the possibility for improving the performance of dye sensitized solar cell (DSSC) only by minimizing the loss in fill factor (FF) and maximum power point (PMAX) which can be achieved by passivating the nanocrystalline titanium dioxide (TiO2) using physical vapor deposited molybdenum trioxide (MoO3) thin films. The effect of MoO3 coated TiO2 on charge carrier transport was examined in resulting DSSCs and observed that  ∼14% enhancement in efficiency is possible for 5 min passivation of MoO3 on TiO2. The physical vapor deposited MoO3 films were  ∼75% transparent in the spectral range of 350–800 nm with an optical bandgap of  ∼3.1 eV. The wide bandgap MoO3 films facilitate the incoming photons to reach the sensitizing dye to generate excitons. The 14% enhancement in the performance of DSSC by MoO3 passivation is observed through improving only the FF and PMAX while it does not contribute anything significantly to current density and open circuit voltage. Electrochemical impedance spectroscopic studies further confirmed these observations through photo-electron lifetime, which remains constant both in the bulk of pristine TiO2 and MoO3 passivated TiO2 and it further confirms the effect of MoO3 passivation on FF and PMAX in DSSCs.

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2018

Journal Article

A. Ashok, Vijayaraghavan, S. N., Unni, G. E., Shantikumar V Nair, and Dr. Mariyappan Shanmugam, “On the Physics of Dispersive Electron Transport Characteristics in SnO 2 Nanoparticle-based Dye Sensitized Solar Cells”, Nanotechnology, vol. 29, p. 175401, 2018.[Abstract]


The present study elucidates dispersive electron transport mediated by surface states in tin oxide (SnO 2 ) nanoparticle-based dye sensitized solar cells (DSSCs). Transmission electron microscopic studies on SnO 2 show a distribution of ∼10 nm particles exhibiting (111) crystal planes with inter-planar spacing of 0.28 nm. The dispersive transport, experienced by photo-generated charge carriers in the bulk of SnO 2 , is observed to be imposed by trapping and de-trapping processes via SnO 2 surface states present close to the band edge. The DSSC exhibits 50% difference in performance observed between the forward (4%) and reverse (6%) scans due to the dispersive transport characteristics of the charge carriers in the bulk of the SnO 2 . The photo-generated charge carriers are captured and released by the SnO 2 surface states that are close to the conduction band-edge resulting in a very significant variation; this is confirmed by the hysteresis observed in the forward and reverse scan current–voltage measurements under AM1.5 illumination. The hysteresis behavior assures that the charge carriers are accumulated in the bulk of electron acceptor due to the trapping, and released by de-trapping mediated by surface states observed during the forward and reverse scan measurements

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2018

Journal Article

G. Gopakumar, Menon, H., Ashok, A., Shantikumar V. Nair, and Dr. Mariyappan Shanmugam, “Two Dimensional Layered Electron Transport Bridges in Mesoscopic TiO2 for Dye Sensitized Solar Cell Applications”, Electrochimica Acta, vol. 267, pp. 63 - 70, 2018.[Abstract]


The present work demonstrates the possibility of facilitating electron transport in mesoscopic titanium dioxide (TiO2) by incorporating nanoflakes of layered molybdenum disulfide (MoS2) as an alternate electron transport bridge. Results suggest that performance of dye sensitized solar cells (DSSCs) can be increased up to ∼16% (from 7.39% to 8.55%) by incorporating 0.2 wt % of MoS2 into the bulk of TiO2, due to the significant improvement in electron lifetime from 8 ms to 23 ms. The nanoflakes of MoS2 form alternate electron transport bridges in the bulk TiO2 nanoparticle film through which photo-injected electrons travel more efficiently to reach transparent electrode compared to DSSCs utilize only TiO2 without MoS2. Presence of atomically thin layered MoS2 nanoflakes in the bulk of TiO2 assist the photo-electrons to skip electron-hole capture processes occur through TiO2 surface states to avoid the interfacial recombination. Further increment in the concentration of MoS2 suppresses the resulting DSSC performance by blocking the porosity which results in less dye adsorption and hence lower photocurrent values

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2018

Journal Article

N. Vikkath, Ariyannur, P., Menon, K. N., Mr, B., and Pillai, A., “Exploring the role of defective fibronectin matrix assembly in the VHL-associated CNS hemangioblastoma.”, Drug Metab Pers Ther, vol. 33, no. 3, pp. 127-134, 2018.

2018

Journal Article

S. Deepthi and Jayakumar, R., “Alginate nanobeads interspersed fibrin network as forming hydrogel for soft tissue engineering.”, Bioact Mater, vol. 3, no. 2, pp. 194-200, 2018.[Abstract]


Hydrogels are a class of materials that has the property of injectability and gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200-500 nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19 kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.

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2018

Journal Article

J. Joseph, Krishnan, A. G., Cherian, A. M., Rajagopalan, B., Jose, R., Varma, P., Maniyal, V., Balakrishnan, S., Nair, S. V., and Menon, D., “Transforming Nanofibers into Woven Nanotextiles for Vascular Application”, ACS Applied Materials and Interfaces, vol. 10, pp. 19449-19458, 2018.[Abstract]


This study investigates the unique properties, fabrication technique, and vascular applications of woven nanotextiles made from low-strength nanoyarns, which are bundles of thousands of nanofibers. An innovative robotic system was developed to meticulously interweave nanoyarns in longitudinal and transverse directions, resulting in a flexible, but strong woven product. This is the only technique for producing seamless nanotextiles in tubular form from nanofibers. The porosity and the mechanical properties of nanotextiles could be substantially tuned by altering the number of nanoyarns per unit area. Investigations of the physical and biological properties of the woven nanotextile revealed remarkable and fundamental differences from its nonwoven nanofibrous form and conventional textiles. This enhancement in the material property was attributed to the multitude of hierarchically arranged nanofibers in the woven nanotextiles. This patterned woven nanotextile architecture leads to a superhydrophilic behavior in an otherwise hydrophobic material, which in turn contributed to enhanced protein adsorption and consequent cell attachment and spreading. Short-term in vivo testing was performed, which proved that the nanotextile conduit was robust, suturable, kink proof, and nonthrombogenic and could act as an efficient embolizer when deployed into an artery. © 2018 American Chemical Society.

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2018

Journal Article

M. N. Sundaram, V. Kaliannagounder, K., Selvaprithiviraj, V., Suresh, M., Biswas, R., Vasudevan, A. K., Varma, P. K., and Dr. Jayakumar Rangasamy, “Bioadhesive, Hemostatic, and Antibacterial in Situ Chitin-Fibrin Nanocomposite Gel for Controlling Bleeding and Preventing Infections at Mediastinum”, ACS Sustainable Chemistry and Engineering, vol. 6, pp. 7826-7840, 2018.[Abstract]


Mediastinitis occurs after cardiac surgery and is a major threat to patient's life due to postoperative bleeding and deep sternal wound infection. Major challenge in treating this condition is that it demands a material that should adhere to the applied site and act as both a hemostatic and an antibacterial agent. On the basis of this we have developed an in situ forming tissue adhesive chitin-fibrin (CH-FB) gel with tigecycline loaded gelatin nanoparticles (tGNPs) for controlling bleeding and preventing bacterial infection. Spherical shaped tGNPs (231 ± 20 nm) were prepared and characterized. In situ forming tGNPsCH-FB gel was formed using a dual syringe applicator in which one syringe was loaded with a mixer of fibrinogen solution, chitin gel, and tGNPs; the other syringe was loaded with a mixture of thrombin solution, chitin gel, and tGNPs. Both these mixtures were injected together. In situ gel formed within a minute and exhibited excellent tissue adhesive property. tGNPsCH-FB gel was found to be cyto-compatible against human umbilical vein endothelial cells (HUVECs). Sustained release of tigecycline from tGNPsCH-FB gel was found to occur over 21 days. In vitro antibacterial activity of tGNPsCH-FB gel was tested against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli), and their clinical isolates. Furthermore, in vivo hemostatic potential of tGNPsCH-FB gel was evaluated in deep organ injuries created in Sprague-Dawley rats. The developed gel exhibited rapid blood clotting potential by achieving hemostasis within 154 and 84 s under femoral artery (pressured) and liver (oozing) bleeding conditions. Hence, these findings exhibit the potential application of the developed tGNPsCH-FB gel to adhere at surgical site for controlling bleeding and prevent bacterial infection after cardiac surgery. © 2018 American Chemical Society.

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2018

Journal Article

S. E. Sajeevan, M. Chatterjee, V. Paul, G. Baranwal, V. A. Kumar, C. Bose, A. Banerji, Dr. Bipin G. Nair, B. P. Prasanth, and Dr. Raja Biswas, “Impregnation of Catheters with Anacardic Acid from Cashew nut Shell Prevents Staphylococcus aureus Biofilm Development.”, Journal of Applied Microbiology, vol. 125, no. 5, pp. 1286-1295, 2018.[Abstract]


AIM: The effect of anacardic acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated. METHODS AND RESULTS: Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0·002-0·25%). Anacardic acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic acid-impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids was observed for 4 days. Anacardic acid-impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of anacardic acid-impregnated catheters was tested in an intraperitoneal catheter-associated medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid-impregnated catheter tubes was observed.

CONCLUSIONS: Our data suggest that anacardic acid-impregnated silicon catheters may help in preventing catheter-related staphylococcal infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens new directions for designing antimicrobial phytochemical-coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists.

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2018

Journal Article

R. Yegappan, Selvaprithiviraj, V., Amirthalingam, S., and Dr. Jayakumar Rangasamy, “Carrageenan Based Hydrogels for Drug Delivery, Tissue Engineering and Wound Healing”, Carbohydrate Polymers, vol. 198, pp. 385-400, 2018.[Abstract]


Carrageenan is a class of naturally occurring sulphated polysaccharides, which is currently a promising candidate in tissue engineering and regenerative medicine as it resemblances native glycosaminoglycans. From pharmaceutical drug formulations to tissue engineered scaffolds, carrageenan has broad range of applications. Here we provide an overview of developing various forms of carrageenan based hydrogels. We focus on how these fabrication processes has an effect on physiochemical properties of the hydrogel. We outline the application of these hydrogels not only pertaining to sustained drug release but also their application in bone and cartilage tissue engineering as well as in wound healing and antimicrobial formulations. Administration of these hydrogels through various routes for drug delivery applications has been critically reviewed. Finally, we conclude by summarizing the current and future outlook that promotes the seaweed-derived polysaccharide as versatile, promising biomaterial for a variety of bioengineering applications. © 2018 Elsevier Ltd.

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2018

Journal Article

S. Xavier, Sundaram, K. R., Biswas, L., Panikar, D., Rajamma, B. M., Nair, S., Krishnakumar N. Menon, and Dr. Lakshmi Sumitra, “Molecular Analysis of Oncogene Expressions in Different Grades of Gliomas”, Journal of Integrated OMICS, vol. 8, pp. 66-73, 2018.[Abstract]


The aggressiveness of brain tumors is attributed to the expression of multiple oncogenes involved in proliferation, metabolism and therapeutic resistance whose potential correlation with tumor progression has not been well-studied. In this study, we aimed to investigate the relationship of oncotargets involved in pathogenesis with respect to glioma grades. Gliomas (n=40) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing for the detection of epidermal growth factor receptor (EGFR) mutants. Expressions levels of EGFRy EGFR variant III (EGFRvIII), Lek/Yes novel tyrosine kinase (Lyn), Spleen tyrosine kinase (SYK), insulin receptor substrate 1 (IRSl)y phosphatidylinositol 3-kinase (PI3K), Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) and glucose transporter 3 (GLUT3) were studied using real-time PCR and compared against glioma grades via statistical methods. Protein expressions were analyzed using immunohistochemistry and western blotting. EGFRvIII was detected in 53% and exon 4 deletion (de4 EGFR) in 20% of gliomas. Importantly, the expressions levels of candidate oncogenes were significantly upregulated (P&lt;0.05) and positively correlated with the glioma grades. Hence, these oncotargets require high surveillance during tumor progression and further investigations on larger patient cohorts can affirm their role as potential markers in the pathology of glioma, thereby aiding in the development of patient-specific multi-targeted therapy. © 2018, Proteomass Scientific Society. All rights reserved.

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2018

Journal Article

A. R. Melge, Prakash, O., S, S., Biswas, R., Biswas, L., and C., G. M., “Structure-function studies of prothrombin Amrita, a dysfunctional prothrombin characterized by point mutation at Arg553 → Gln”, International Journal of Biological Macromolecules, vol. 110, pp. 550-557, 2018.[Abstract]


A dysfunctional prothrombin gene characterized by novel point mutation at Arg553 to Gln residue in Deep vein thrombosis (DVT) patient which we designated as “Prothrombin Amrita” was previously reported from our lab. The mutation occurred at nucleotide 20030 in exon 14 and was confirmed by restriction enzyme digestion. Arg553 has been reported as one of the key residues for the binding of cofactor Na+ ion in the thrombin protein. Structural analysis revealed the molecular mechanism behind the coagulant form of thrombin due to point Arg553Gln mutation near the cofactor Na+ ion region. Molecular electrostatic potential maps and molecular dynamics (MD) simulation of the wild type and mutated thrombin showed the key role played by the Na+ ion for its coagulant mechanism by analysing the charge distribution and nature of the hydrogen bonding at the mutated region of interest. We observed maintenance of the fast or procoagulant form of dysfunctional prothrombin due to changes in the charge distribution by this mutation and thereby also keeping strong hydrogen bonding network revealed by MD simulation between prothrombin and Na+ ion. This molecular mechanism might be the main cause for DVT in patients with this dysfunctional prothrombin gene. © 2018 Elsevier B.V. More »»

2018

Journal Article

V. Aparna, Melge, A. Rohit, Rajan, V. K., Raja Biswas, Dr. Jayakumar Rangasamy, and C. Mohan, G., “Carboxymethylated ɩ-carrageenan Conjugated Amphotericin B loaded Gelatin Nanoparticles for Treating Intracellular Candida Glabrata Infections”, International Journal of Biological Macromolecules, vol. 110, pp. 140 - 149, 2018.[Abstract]


Intercellular Candida glabrata infections are difficult to treat due to poor penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B) into the macrophages where the pathogen inhabits is an effective solution. We are studying the macrophage targeting proficiency of ɩ-carrageenan for the delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A was the outcome of in silico inspections where the amino functionalized polymer having the best docking score with Amp B was selected. We prepared a sustained release formulation of amp B loaded carboxymethyl ɩ-carrageenan conjugated gelatin nanoparticles (CMC-Amp B-GNPs) with size 343±12nm and −25±5.3mV zeta potential. The formulations were found to be stable, biocompatible and non-haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced antifungal activity than bare Amp B and Amp B-GNPs.

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2018

Journal Article

K. Parvathi, Krishnan, A. G., Anitha, A., Dr. Jayakumar Rangasamy, and Nair, M. B., “Poly(L-lactic acid) Nanofibers containing Cissus Guadrangularis induced Osteogenic Differentiation in Vitro”, International Journal of Biological Macromolecules, vol. 110, pp. 514 - 521, 2018.[Abstract]


Cissus quadrangularis (CQ) is known as “bone setter” in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications

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2018

Journal Article

S. Deepthi and Dr. Jayakumar Rangasamy, “Alginate Nanobeads Interspersed Fibrin Network as in Situ Forming Hydrogel for Soft Tissue Engineering”, Bioactive Materials, vol. 3, pp. 194 - 200, 2018.[Abstract]


Hydrogels are a class of materials that has the property of injectability and in situ gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200–500&nbsp;nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the in situ injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19&nbsp;kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed in situ forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.

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2018

Journal Article

A. Mohandas, Deepthi, S., Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Chitosan Based Metallic Nanocomposite Scaffolds as Antimicrobial Wound Dressings”, Bioactive Materials, vol. 3, pp. 267 - 277, 2018.[Abstract]


Chitosan based nanocomposite scaffolds have attracted wider applications in medicine, in the area of drug delivery, tissue engineering and wound healing. Chitosan matrix incorporated with nanometallic components has immense potential in the area of wound dressings due to its antimicrobial properties. This review focuses on the different combinations of Chitosan metal nanocomposites such as Chitosan/nAg, Chitosan/nAu, Chitosan/nCu, Chitosan/nZnO and Chitosan/nTiO2 towards enhancement of healing or infection control with special reference to the antimicrobial mechanism of action and toxicity.

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2018

Journal Article

A. Mohandas, Sun, W., Nimal, T. R., Shankarappa, S. A., Hwang, N. S., and Dr. Jayakumar Rangasamy, “Injectable chitosan-fibrin/nanocurcumin composite hydrogel for the enhancement of angiogenesis”, Research on Chemical Intermediates, vol. 44, pp. 4873–4887, 2018.[Abstract]


The work focuses on the development of an injectable chitosan-fibrin (CF) based nanocomposite hydrogel for angiogenic response. The hydrogel base is made of chitosan gel, 3{%} (wt/wt) of which is composed of fibrin. The injectable nanocomposite gel was prepared by incorporating nanocurcumin (nC) 100–150&nbsp;nm in size, with a zeta potential of +&nbsp;33.5&nbsp;±&nbsp;3&nbsp;mV into the CF hydrogel. The gel was characterized by scanning electron microscopy and rheometry for the morphological and visco-elastic properties. Furthermore, cytocompatibility and angiogenic response of the CF hydrogel was analyzed with human umbilical cord vein endothelial cells. In vitro tube formation and nitric oxide release assay revealed the improved angiogenic behavior of the nanocomposite hydrogel when compared to the control. Further, angiogenesis was confirmed by ex vivo aortic sprouting assay. These studies suggest that the developed injectable chitosan-fibrin/nanocurcumin (CF/nC) hydrogel can be used for angiogenic stimulation

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2018

Journal Article

A. Gopalakrishnan, Shankarappa, S. A., and Rajanikant, G. K., “Hydrogel Scaffolds: Towards Restitution of Ischemic Stroke-Injured Brain.”, Transl Stroke Res, 2018.[Abstract]


Chronic brain injury following cerebral ischemia is a severe debilitating neurological condition, where clinical intervention is well known to decrease morbidity and mortality. Despite the development of several therapeutic strategies, clinical outcome in the majority of patients could be better improved, since many still face life-long neurological deficits. Among the several strategic options that are currently being pursued, tissue engineering provides much promise for neural tissue salvage and regeneration in brain ischemia. Specifically, hydrogel biomaterials have been utilized to docket biomolecules, adhesion motifs, growth factors, and other proneural cues for stable stem cell encapsulation. Here, we provide an overview of therapeutic applications of hydrogels in stroke treatment. Special focus is given to design considerations for generation of efficient hydrogel systems for neurological applications. Therapeutic applications of hydrogels in stroke as conducive microenvironments for stem cell transplantation and drug delivery have been discussed. Finally, we present our perspectives on clinical translation of hydrogels for neural tissue regeneration.

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2018

Journal Article

N. George, M Asokan, A., Ajish, A., Surya, S., Vishnu, V., Pai, R. G., and Zachariah, S. Mary, “Chemistry And Pharmacological Activities Of Biginelli Product- A Brief Overview.”, Curr Drug Discov Technol, 2018.[Abstract]


Dihydropyrimidinones are extremely advantageous small sized molecules owning adaptable pharmaceutical properties. With a molecular formula C4H6N2O, they hold a wide range of biological activities. It is a heterocyclic moiety having two N-atoms at positions 1 and 3. They are derivatives of pyrimidine containing an additional ketone group. They have inspired development of a wide range of synthetic methods for preparation and chemical transformations. Taking into consideration their structural similarity and involvement with DNA and RNA, they have become very imperative in the world of synthetic organic chemistry. Aryl substituted moieties and their derivatives are significant class of substances in medicinal and organic chemistry. Many alkaloids from natural marine sources comprising dihydropyrimidinones core have been isolated which possess fascinating biological properties. Intensive explorations have been carried out on these compounds because they possess close similitude to clinically used nifedipine, nicardipine etc. which are also Biginelli product analogues. Due to the interesting pharmacological properties associated with the privileged DHPM structures, the Biginelli reaction and related procedures have received increasing attention in recent years.

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2018

Journal Article

P. Ponnachan, Vinod, V., Pullanhi, U., Varma, P., Singh, S., Biswas, R., and Kumar, A., “Antifungal Activity of Octenidine Dihydrochloride and Ultraviolet-C light against Multidrug-Resistant Candida auris.”, J Hosp Infect, 2018.[Abstract]


Outbreaks due to multidrug-resistant Candida auris have emerged as a large threat to modern medicine. Since skin colonization and environmental contamination have been identified as a precursor for outbreaks, we evaluated the antifungal activity of ultraviolet-C light using mercury vapor lamp with a peak emission of 254±2 nm and octenidine dihydrochloride against C. auris clinical isolates. Octenidine dihydrochloride was found effective at significantly lower concentrations (0.00005-0.0004%) than those currently used in the clinical setting (0.05% to 0.1%). Scanning electron microscopy images show destruction of the organism within 6 hours of exposure to 0.0005% octenidine dihydrochloride. Ultraviolet-C light could kill all C. auris with 15 minutes exposure.

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2018

Journal Article

M. Vijayamohan, A, A., Menon, D., Iyer, S., Shantikumar V Nair, and Nair, M., “Nanofibrous yarn Reinforced HA-gelatin Composite Scaffolds Promote Bone Formation in Critical Sized Alveolar Defects in Rabbit Model”, Biomed Mater, 2018.[Abstract]


Alveolar ridge resorption and crestal bone loss commonly necessitate the use of bone graft substitutes for dental rehabilitation. The aim of this study was to compare the bone regenerative property of two nanofibre incorporated composite matrices [Nanofibrous sheet layered matrix (CS-S) and nanofibrous yarn reinforced matrix (CS-Y)] in critical sized mandibular defect in a rabbit model (under load bearing scenario). Histological evaluation revealed continuous bone formation in the defect implanted with fibre reinforced scaffolds than those without fibers as well as commercial nanoHA-collagen graft. Interestingly, the mineralisation and the mineral density were significantly higher in the defect with nanoyarn reinforced scaffolds. Moreover, the compressive strength of new bone formed from CS-Y scaffolds was almost similar to that of native rabbit mandible. It can be concluded that the mechanical strength provided by three-dimensionally reinforced nanoyarns in the matrix could promote bone formation in load bearing mandibular region, and these can be proposed as a scaffold of choice for alveolar bone augmentation and dental rehabilitation.

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2018

Journal Article

S. Kuttappan, Mathew, D., Jo, J. - I., Tanaka, R., Menon, D., Ishimoto, T., Nakano, T., Nair, S. V., Nair, M. B., and Tabata, Y., “Dual release of growth factor from nanocomposite fibrous scaffold promotes vascularisation and bone regeneration in rat critical sized calvarial defect.”, Acta Biomater, vol. 78, pp. 36-47, 2018.[Abstract]


A promising strategy for augmenting bone formation involves the local delivery of multiple osteoinductive and vasculogenic growth factors. However, success depends on sustained growth factor release and its appropriate combination to induce stem cells and osteogenic cells at the bony site. Herein, we have developed a nanocomposite fibrous scaffold loaded with fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) and its ability to promote vascularisation and bone regeneration in critical sized calvarial defect was compared to the scaffold with VEGF + BMP2 and FGF2 + BMP2. Simple loading of growth factors on the scaffold could provide a differential release pattern, both in vitro and in vivo (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks). Among all the groups, dual growth factor loaded scaffold (VEGF + BMP2 & FGF2 + BMP2) enhanced vascularisation and new bone formation, but there was no difference between FGF2 and VEGF loaded scaffolds although its release pattern was different. FGF2 mainly promoted stem cell migration, whereas VEGF augmented new blood vessel formation at the defect site. This study suggests that biomimetic nanocomposite scaffold is a promising growth factor delivery vehicle to improve bone regeneration in critical sized bone defects.

STATEMENT OF SIGNIFICANCE: Many studies have shown the effect of growth factors like VEGF-BMP2 or FGF2-BMP2 in enhancing bone formation in critical sized defects, but there are no reports that demonstrate the direct comparison of VEGF-BMP2 and FGF2-BMP2. In this study, we have developed a nanocomposite fibrous scaffold that could differentially release growth factors like VEGF, BMP2 and FGF2 (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks), which in turn promoted neovascularisation and new bone formation in critical sized defects. There was no difference in vascularisation and bone formation induced by VEGF + BMP2 or FGF2 + BMP2. The growth factor was loaded in a simple manner, which would ensure ease of use for the end-user, especially for the surgeons treating a patient in an operating room.

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2018

Journal Article

A. Mohandas, Deepthi, S., Biswas, R., and Jayakumar, R., “Chitosan based metallic nanocomposite scaffolds as antimicrobial wound dressings.”, Bioact Mater, vol. 3, no. 3, pp. 267-277, 2018.[Abstract]


Chitosan based nanocomposite scaffolds have attracted wider applications in medicine, in the area of drug delivery, tissue engineering and wound healing. Chitosan matrix incorporated with nanometallic components has immense potential in the area of wound dressings due to its antimicrobial properties. This review focuses on the different combinations of Chitosan metal nanocomposites such as Chitosan/nAg, Chitosan/nAu, Chitosan/nCu, Chitosan/nZnO and Chitosan/nTiO towards enhancement of healing or infection control with special reference to the antimicrobial mechanism of action and toxicity.

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2018

Journal Article

N. M Sundaram, Deepthi, S., Mony, U., Shalumon, K. T., Chen, J. - P., and Dr. Jayakumar Rangasamy, “Chitosan hydrogel scaffold reinforced with twisted poly(l lactic acid) aligned microfibrous bundle to mimic tendon extracellular matrix.”, Int J Biol Macromol, 2018.[Abstract]


Regeneration of tendon requires construct that provides necessary structural support closely mimicking the native architecture. To recreate this complex architecture a construct made of heat-treated, twisted poly(L lactic acid) (PLLA) microfibers coated with chitosan gel and surrounded by PLLA micro-fibrous layer was developed. The developed construct characterized using SEM showed the macroporous nature of gel coating around four distinct PLLA twisted fibrous bundle and a thin fiber layer surrounding the construct. FTIR analysis confirmed the presence of PLLA and chitosan construct. Mechanical strength increased with increasing number of strips. Protein adsorption was significantly low on the construct with outer covering that could retard cell adhesion to the outer layer. The developed construct showed good cell attachment and proliferation of tenocytes. These results indicate that the construct would find application for tendon tissue engineering.

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2018

Journal Article

S. Kuttappan, Mathew, D., Jo, J. - I., Tanaka, R., Menon, D., Ishimoto, T., Nakano, T., Nair, S. V., Nair, M. B., and Tabata, Y., “Dual release of growth factor from nanocomposite fibrous scaffold promotes vascularisation and bone regeneration in rat critical sized calvarial defect”, Acta Biomaterialia, vol. 78, pp. 36-47, 2018.[Abstract]


A promising strategy for augmenting bone formation involves the local delivery of multiple osteoinductive and vasculogenic growth factors. However, success depends on sustained growth factor release and its appropriate combination to induce stem cells and osteogenic cells at the bony site. Herein, we have developed a nanocomposite fibrous scaffold loaded with fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) and its ability to promote vascularisation and bone regeneration in critical sized calvarial defect was compared to the scaffold with VEGF + BMP2 and FGF2 + BMP2. Simple loading of growth factors on the scaffold could provide a differential release pattern, both in vitro and in vivo (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks). Among all the groups, dual growth factor loaded scaffold (VEGF + BMP2 & FGF2 + BMP2) enhanced vascularisation and new bone formation, but there was no difference between FGF2 and VEGF loaded scaffolds although its release pattern was different. FGF2 mainly promoted stem cell migration, whereas VEGF augmented new blood vessel formation at the defect site. This study suggests that biomimetic nanocomposite scaffold is a promising growth factor delivery vehicle to improve bone regeneration in critical sized bone defects. Statement of Significance: Many studies have shown the effect of growth factors like VEGF-BMP2 or FGF2-BMP2 in enhancing bone formation in critical sized defects, but there are no reports that demonstrate the direct comparison of VEGF-BMP2 and FGF2-BMP2. In this study, we have developed a nanocomposite fibrous scaffold that could differentially release growth factors like VEGF, BMP2 and FGF2 (VEGF release for 1 week where as BMP2 and FGF2 release for 3 weeks), which in turn promoted neovascularisation and new bone formation in critical sized defects. There was no difference in vascularisation and bone formation induced by VEGF + BMP2 or FGF2 + BMP2. The growth factor was loaded in a simple manner, which would ensure ease of use for the end-user, especially for the surgeons treating a patient in an operating room. © 2018 Acta Materialia Inc.

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2018

Journal Article

A. R. Melge, Kumar, L. G., K, P., Nair, S. V., K, M., and C Mohan, G., “Predictive Models for Designing Potent Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia for Understanding its Molecular Mechanism of Resistance by Molecular Docking and Dynamics Simulations.”, J Biomol Struct Dyn, pp. 1-68, 2018.[Abstract]


BCR-ABL fusion protein drives chronic myeloid leukaemia (CML) which constitutively activates tyrosine kinase involved in the initiation and maintenance of CML phenotype. Ponatinib, an oral drug was discovered as an efficient BCR-ABL inhibitor by addressing imatinib drug resistance arising due to the point mutations at its active sites. In this study, 44 BCR-ABL kinase inhibitors, which are derivatives of ponatinib were used to develop a robust 2D-QSAR and 3D-Pharmacophore models by dividing dataset into 32 training set and 12 test set molecules. 2D-QSAR model was developed using Genetic Function Approximation (GFA) algorithm consisting of four types of information rich molecular descriptors, electro-topological (ES_Count_aasN and ES_Sum_aaaC), electronic (Dipole_X), spatial (PMI_Y) and thermodynamic (Log D), primarily contributing to BCR-ABL kinase inhibitory activity. For best 2D-QSAR model, the statistics were R =0.8707, R =0.8142, N = 32 for the training set molecules. Phase module of Schrödinger suit was employed for 3D-Pharmacophore model development showing five different pharmacophoric features- ADHHPRR with good R 0.9629, F 175.3, Q 0.645 and RMSE of 0.214 that are essential for an effective BCR-ABL kinase inhibition. These two models were further validated by cross-validation, test set predictions, enrichment factor calculations and predictions based on the external data set. The molecular mechanism of resistance arising due to gate keeper mutation T315I of ABL kinase in complex with its inhibitors was also studied using molecular docking and molecular dynamics simulations. Our developed models predicted key chemical features for designing potent inhibitors against BCR-ABL kinase activity and its resistance mechanism to CML disease therapy.

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2018

Journal Article

P. Sagitha, Reshmi, C. R., Sundaran, S. P., Anupama Binoy, Dr. Nandita Mishra, and Sujith, A., “In-vitro evaluation on drug release kinetics and antibacterial activity of dextran modified polyurethane fibrous membrane.”, International Journal of Biological Macromolecules, vol. 126, pp. 717-730, 2018.[Abstract]


pH stimuli drug release nanofibrous membranes of polyurethane/dextran were developed for tailoring of antibacterial wound dressings. Incorporation of dextran in polyurethane (PU) showed increment in hydrophilicity, vapour transmission rate, percentage sorption values, and biodegradability. Dextran also acts as reinforcement filler in PU matrix. Dextran induces a high degree of platelet adhesion and hemostasis potential which is essential for promoting the wound healing process. Moreover, 20 wt% dextran loaded membranes (PU/20D) exhibited enhanced cell proliferation, attachment and viability against 3T3 fibroblasts. Curcumin loaded PU/20 dextran membrane exhibited pH-controlled drug release potency and synergistic antibacterial activity against gram-positive bacteria. It is confirmed that, PU/20D membranes could promote, pH-controlled drug release and synergistic antibacterial activity for a promising wound dressing material.

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2018

Journal Article

A. P. Varghese, Nair, S., and Santhanagopalan, D., “Cobalt oxide thin films for high capacity and stable Li-ion battery anode”, Journal of Solid State Electrochemistry, 2018.[Abstract]


Here, we report reactive DC-sputter deposited Co3O4 thin films as a promising and stable Li-ion battery anode. Thin films were deposited on stainless steel by reactive sputtering of cobalt target in O2 atmosphere. X-ray diffraction and X-ray photo electron spectroscopy confirm the formation of Co3O4 crystal structure and absence of other impurities. The electron microscopy analysis shows a columnar growth morphology of the thin films while high resolution images reveal that the film is composed of ultra-small nanoparticles of average size of 5 nm. Fabricated half cells upon cycling between 3.0 and 0.01 V exhibit a stable capacity of 1125 mAh/g at a current density of 1 A/g for 100 cycles. Moreover, the electrode exhibited excellent rate capability and stability at higher rates; at current density of 10 A/g, a capacity close to 1000 mAh/g was observed. The excellent cycling stability of the cell was further confirmed by cycling at a high rate of 25 A/g (28 C) wherein the same was able to retain a capacity of 330 mAh/g even at the end of 1800 cycles. This enhanced performance could be related to the formation of 5-nm primary particles and columnar growth morphology, capable of reducing the lithium ion diffusion lengths and thus offered better kinetics even at high rates. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

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2018

Journal Article

M. K. Suresh, Biswas, R., and Biswas, L., “An update on recent developments in the prevention and treatment of Staphylococcus aureus biofilms”, International Journal of Medical Microbiology, 2018.[Abstract]


Staphylococcus aureus (S. aureus) readily forms biofilms on prosthetic devices such as the pacemakers, heart valves, orthopaedic implants, and indwelling catheters. Its biofilms are recalcitrant to antibiotic therapy and pose a serious burden in the healthcare setting as they drastically increase the treatment cost and morbidity of the patient. Prevention and treatment of staphylococcal biofilms has therefore been an area of active research for the past two decades. While catheters coated with different antiseptics and antibiotics capable of preventing S. aureus biofilm formation have been developed, an effective therapy for the dispersal and treatment of established staphylococcal biofilms is not yet available. Hence, many studies have focused on developing novel therapeutic strategies that can tackle established S. aureus biofilm associated infections. This has led to the identification of different phytochemicals (e.g., tannic acid, ellagic acid, xanthohumol etc), enzymes (e.g., Dnases, lysostaphin, α-amylase, hyaluronidase and proteases etc.), sulfahydrl compounds (e.g., dithiothreitol, 2-mercaptoethanol), nanoparticles (e.g., gold, silver, iron, copper and selenium), phage cocktails, antibodies and metal chelators. Apart from the conventional techniques, the therapeutic effects of ultra sound, shock waves and photodynamic therapy for treating S. aureus biofilms are also being investigated. Clinical validation of these studies will equip the medical field with alternate preventive and treatment methods against staphylococcal biofilm infections. This review provides recent updates on the preventive and therapeutic strategies explored to eradicate staphylococcal biofilm formation and related infections. © 2018

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2018

Journal Article

A. Baldi, Mooij, L., Palmisano, V., Schreuders, H., Dr. Gopi Mohan C., Kooi, B. J., Dam, B., and Griessen, R., “Elastic versus Alloying Effects in Mg-Based Hydride Films”, Phys. Rev. Lett., vol. 121, p. 255503, 2018.

2018

Journal Article

B. Gangaja, Jayasree, S. S., Shantikumar V Nair, and Santhanagopalan, D., “Effect of Lithiation Voltage Limit on the Electrochemical Performance of High Surface Area Anatase TiO2 Nanoparticles and Its Application in Full-Cell Li–Ion Battery”, ChemistrySelect, vol. 3, pp. 12258-12262, 2018.[Abstract]


Abstract Titania based anodes have received considerable interest due to its cycling stability and improved safety. Here, we report the electrochemical performance of high surface area anatase TiO2 nanoparticles synthesized via solvothermal technique. Prepared anatase TiO2 nanoparticles were below 15 nm in average particle size exhibiting high surface area of 251 m2/g and titanium existing in 4+ oxidation state. The electrodes studied by limiting the discharge voltage between 1.0 V and 0.01 V showed significant performance differences. Especially, specific capacity, Coulombic efficiency and storage mechanism of TiO2 depends strongly on lithiation voltage cut-off limit that is discussed in detail. It was established that discharging to 1.0 V showed better performance hence, subsequent studies the lithiation (discharge) was limited to 1.0 V. High rate capability of the electrodes were tested test up to 60 C and long cycle stability up to 1000 cycles (at 10 C rate). As an energy storage solution, a&nbsp;2.0 V full-cell Li-ion battery was fabricated with the TiO2 nanoparticles as anode against surface modified LiCoO2 as cathode. The full-cell delivered specific capacities about 165 mAh/g and 105 mAh/g at current densities of 150 mA/g and 3765 mA/g respectively. It also exhibited 126 mAh/g capacity and 85% retention at the end of 100 cycles at a current density of 1000 mA/g. The full-cell delivered a maximum power density of 5.5 kW/kg and a corresponding energy density of 185 Wh/kg.

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2018

Journal Article

M. Benny, Gangaja, B., Shantikumar V Nair, and Santhanagopalan, D., “Electrosprayed NiCo2O4 Nanoparticles for Long Cycle life and High-power Li-ion Battery Anode”, Ionics, vol. 24, pp. 3375–3383, 2018.[Abstract]


Electrospraying-based synthesis of NiCo2O4 (NCO-ES) nanoparticles that exhibit long cycle life and high rate capability is reported. The results are compared with a conventionally prepared NiCo2O4 sample by direct annealing (NCO-DA). The structure and morphology of NCO-ES and NCO-DA nanoparticles have been characterized by X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy to confirm the size, morphology, structure, and surface chemistry of the as-prepared samples. Electrochemical testing established that the NCO-ES sample displayed enhanced Li-ion storage performance. The NCO-ES delivered a discharge capacity of almost 370&nbsp;mAh/g at the end of 50 cycles at 1C rate (890&nbsp;mA/g) while only 180&nbsp;mAh/g was retained for the NCO-DA sample at the same condition. At a high rate of 5C (4450&nbsp;mA/g), NCO-ES electrodes delivered a stabilized specific capacity of 225&nbsp;mAh/g with almost 100{%} Coulombic efficiency over 1000 cycles. Its rate capability and cycle life were found to be superior to NCO-DA electrodes. The nanoscale grain boundaries in the NCO-ES sample enhanced the lithium-ion diffusion and enabled high rate capability. The impedance analysis at different stages of lithiation/delithiation indicates a lower impedance and better kinetics as one of the reasons for better performance of the NCO-ES sample.

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2018

Journal Article

S. Suresh, Unni, G. E., Satyanarayana, M., A. Nair, S., and Pillai, V. P. Mahadevan, “Plasmonic Ag@Nb2O5 Surface Passivation Layer on Quantum Confined SnO2 Films for High Current Dye-sensitized Solar Cell Applications”, Electrochimica Acta, vol. 289, pp. 1 - 12, 2018.[Abstract]


Quantum-confined SnO2 nanoparticles of size &lt;6 nm are synthesized by a hydrothermal process and these nanoparticles are dispersed in a colloidal solution to deposit onto transparent conductive glasses (FTO) via spray-pyrolysis deposition (SPD) technique. The spray-pyrolysis deposited SnO2 films are used as photoanode in dye-sensitized solar cells (DSSCs). Very high current and improved conversion efficiencies are the characteristic of these SnO2 solar cells compared to those from literature. Applying an Nb2O5 energy layer on top of SnO2 films via RF sputtering resulted in an improvement in performance of these solar cells. Ag nanoparticle/Nb2O5 composite is applied as plasmonic surface passivation layer on SnO2 photoanodes which improved the absorption spectra of the dye-sensitized photoanodes and the current density (17.44–23.12 mA/cm2) and power conversion efficiencies (4.36%–6.47%) of the DSSCs. This article thus focuses on synthesis and quantum confinement properties of SnO2 nanoparticles, the effect of Nb2O5 and Ag nanoparticles on the optical and electronic properties of the SnO2 photoanodes and finally the photovoltaic properties of the SnO2 photoanodes with Nb2O5/Ag-Nb2O5 surface passivation layers.

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2018

Journal Article

S. Kwon, Lee, S. S., Sivashanmugam, A., Kwon, J., Kim, S. Hyun L., Noh, M. Yeon, Kwon, S. Keun, Dr. Jayakumar Rangasamy, and Hwang, N. S., “Bioglass-Incorporated Methacrylated Gelatin Cryogel for Regeneration of Bone Defects”, Polymers, vol. 10, 2018.[Abstract]


Cryogels have recently gained interest in the field of tissue engineering as they inherently possess an interconnected macroporous structure. Considered to be suitable for scaffold cryogel fabrication, methacrylated gelatin (GelMA) is a modified form of gelatin valued for its ability to retain cell adhesion site. Bioglass nanoparticles have also attracted attention in the field due to their osteoinductive and osteoconductive behavior. Here, we prepare methacrylated gelatin cryogel with varying concentration of bioglass nanoparticles to study its potential for bone regeneration. We demonstrate that an increase in bioglass concentration in cryogel leads to improved mechanical property and augmented osteogenic differentiation of mesenchymal cells during in vitro testing. Furthermore, in vivo testing in mice cranial defect model shows that highest concentration of bioglass nanoparticles (2.5 w/w %) incorporated in GelMA cryogel induces the most bone formation compared to the other tested groups, as studied by micro-CT and histology. The in vitro and in vivo results highlight the potential of bioglass nanoparticles incorporated in GelMA cryogel for bone regeneration.

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2018

Journal Article

S. N. Vijayaraghavan, Ashok, A., Gopakumar, G., Menon, H., Shantikumar V Nair, and Shanmugam, M., “All Spray Pyrolysis-coated CdTe–TiO2 Heterogeneous Films for Photo-Electrochemical Solar Cells”, Materials for Renewable and Sustainable Energy, vol. 7, p. 12, 2018.[Abstract]


Cadmium telluride (CdTe) thin films of different thicknesses deposited onto titanium dioxide (TiO2) nanoparticle layer by spray pyrolysis deposition (SPD) are demonstrated as major photo-active semiconductor in photo-electrochemical solar cell configuration using iodide/triiodide (I−/I3−) redox couple as a hole transport layer. The CdTe–TiO2 heterogeneous films were characterized by X-ray photoelectron spectroscopy which identified doublet split of Cd 3d and Ti 2p which confirms CdTe and TiO2. Optical absorbance and transmittance of CdTe and TiO2 films which were examined by UV–Vis spectroscopy confirm that the optical bandgap of CdTe is 1.5&nbsp;eV with a dominant photo-absorption in the spectral window of 350–800&nbsp;nm, while TiO2 showed a bandgap of 3.1&nbsp;eV and is optically transparent in the visible spectral window. The present work examined photo-anodes comprising 1, 3, 5, and 10 SPD cycles of CdTe coated on TiO2 nanoparticle layer. The solar cell with 5 SPD cycles of CdTe resulting in 0.4{%} efficiency. Results can be articulated to the CdTe deposited by 5 SPD cycles provided an optimum surface coverage in the bulk of TiO2, while the higher SPD cycles leads to agglomeration which blocks the porosity of the heterogeneous films.

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2018

Journal Article

B. Gangaja, Haridas, A. K., Shantikumar V Nair, and Dr. Dhamodaran Santhanagopalan, “Spray Pyrolysis-Deposited TiO2 Thin Films as High-Performance Lithium ion Battery Anodes”, Ionics, 2018.[Abstract]


Focusing on additive-free electrodes, thin films are of typical interest as electrodes for lithium ion battery application. Herein, we
report the fabrication of TiO2 thin films by spray pyrolysis deposition technique. X-ray diffraction and transmission electron
microscopic analysis confirms the formation of anatase TiO2. Electrochemical evaluation of these sub-micron TiO2 thin films
exhibits high-rate performance and long cycling stability. At 1C rate (1C = 335 mA/g), the electrode delivered discharge capacity
of 247 mAh/g allowing about 0.74 lithium into the structure. The electrodes also delivered specific capacities of 122 and 72 mAh/
g at 10 and 30C rates, respectively. Without conductive additives, this excellent performance can be attributed to the nanosize
effect of TiO2 particles combined with the uniform porous architecture of the electrode. Upon cycling at high rates (10 and 30C),
the electrode exhibited excellent cycling stability and retention, specifically only < 0.6% capacity loss per cycle over 2500 cycles.

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2018

Journal Article

D. Susan Baji, Jadhav, H. S., Shantikumar V Nair, and Alok Kumar Rai, “Porous MnCo2O4 as Superior Anode Material Over MnCo2O4 Nanoparticles for Rechargeable Lithium ion Batteries”, Journal of Solid State Chemistry, vol. 262, pp. 191 - 198, 2018.[Abstract]


Pyro synthesis is a method to coat nanoparticles by uniform layer of carbon without using any conventional carbon source. The resultant carbon coating can be evaporated in the form of CO or CO2 at high temperature with the creation of large number of nanopores on the sample surface. Hence, a porous MnCo2O4 is successfully synthesized here with the same above strategy. It is believed that the electrolyte can easily permeate through these nanopores into the bulk of the sample and allow rapid access of Li+ ions during charge/discharge cycling. In order to compare the superiority of the porous sample synthesized by pyro synthesis method, MnCo2O4 nanoparticles are also synthesized by sol-gel synthesis method at the same parameters. When tested as anode materials for lithium ion battery application, porous MnCo2O4 electrode shows high capacity with long lifespan at all the investigated current rates in comparison to MnCo2O4 nanoparticles electrode

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2018

Journal Article

B. Gangaja, Muralidharan, H. P., Shantikumar V Nair, and Dr. Dhamodaran Santhanagopalan, “Ultralong (10K) Cycle-Life and High-Power Li-Ion Storage in Li4Ti5O12 Films Developed via Sustainable Electrophoretic Deposition Process”, ACS Sustainable Chemistry & Engineering, vol. 6, pp. 4705-4710, 2018.[Abstract]


A critical challenge for Li-ion battery electrodes is to provide high energy density, power density, and excellent cycle-life combined with safety and sustainability. Increasing conductive additive concentration in composite electrodes enables relatively higher power density but compromises energy density. The energy density increment can be attained by fabricating additive-free electrodes, maximizing active mass, while improving the charge transport to maintain high power density is significantly important especially for materials that have inherent conductivity issues (such as Li4Ti5O12). Herein, we demonstrate a nanostructured spinel lithium titanate (LTO) anode which is inherently safe and benign, deposited without additives through a green and scalable electrophoretic deposition (EPD) technique. The electrode is capable of rendering high capacity (160 mA h/g), high rate capability (72C), and excellent cycle-life (10 000 cycles). The outstanding performance in terms of cycle-life, energy, and power is attributed to the formation of electrically interconnected LTO nanoparticle films with porosity enabling better electrolyte percolation and rapid charge transfer. The porous nature of the film is visualized utilizing confocal fluorescence microscopy imaging which confirms the dye impregnation into the bulk of the films as well. The benefit of EPD is due to its potential for sustainability, scalability, rapid deposition rate, simple apparatus, and formation of porous film.

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2018

Journal Article

S. Mohapatra, Shantikumar V Nair, and Rai, A. Kumar, “Synthesis of Co3O4 Nanoparticles Wrapped Within Full Carbon Matrix as an Anode Material for Lithium Ion Batteries”, Acta Metallurgica Sinica (English Letters), vol. 31, pp. 164–170, 2018.[Abstract]


A facile polyol-assisted pyro-synthesis method was used to synthesize Co3O4 nanoparticles embedded into carbon matrix without using any conventional carbon source. The surface analysis by scanning electron microscopy showed that the Co3O4 nanoparticles ({\textasciitilde}20&nbsp;±&nbsp;5&nbsp;nm) are tightly enwrapped within the carbon matrix. CHN analysis determined the carbon content was only 0.11{%} in the final annealed sample. The Co3O4@carbon exhibited high capacities and excellent cycling performance as an anode at various current rates (such as 914.4 and 515.5&nbsp;mAh&nbsp;g−1 at 0.25 and 1.0&nbsp;C, respectively, after 50 cycles; 318.2&nbsp;mAh&nbsp;g−1 at a high current rate of 5.0&nbsp;C after 25 cycles). This superior electrochemical performance of the electrode can be attributed to the various aspects, such as, (1) the existence of carbon matrix, which acts as a flexible buffer to accommodate the volume changes during Li+ ion insertion/deinsertion and facilitates the fast Li+ and electron transfer and (2) the anchoring of Co3O4 nanoparticles within the carbon matrix prevents particles agglomeration.

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2018

Journal Article

S. Suresh, Unni, G. E., Satyanarayana, M., A. Nair, S., and Pillai, V. P. Mahadev, “Ag@Nb2O5 Plasmonic Blocking Layer for Higher Efficiency Dye-sensitized Solar Cells”, Dalton Trans., vol. 47, pp. 4685-4700, 2018.[Abstract]


Engineering photons on a nanoscale via guidance and localization by metal nanostructures has a profound influence on the performance of devices that try to mimic the process of photosynthesis. The conventional route for the synthesis of plasmonic nanoparticles and their integration into the porous structure of the photoanode either directly or after being capped with a dielectric material not only adds to the complexity but also to the cost of the cell. The present study introduces the concept of a plasmonic blocking layer that concurrently acts as a light harvester and an electron-blocking layer in a dye-sensitized solar cell (DSSC){,} wherein the plasmonic silver nanoparticles are incorporated into an Nb2O5 blocking layer by a simple one-step process. The cell with the plasmonic blocking layer achieves an efficiency of 9.24% when compared with a cell with a non-plasmonic blocking layer (7.6%){,} registering an impressive enhancement in the efficiency by 22%. Moreover{,} the cell with the plasmonic blocking layer shows an improvement in the efficiency by 49% when compared with the cell without a blocking layer (6.19%).

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2018

Journal Article

S. H, M, S., M, M., and J.H., M., “Review on Dye-sensitized Solar Cells based on Polymer Electrolytes”, International Journal of Engineering and Technology(UAE), 2018.

2018

Journal Article

Dr. Dhamodaran Santhanagopalan, Benny, M., Binitha, G., and Shantikumar V Nair, “Long Cycle-life and High Rate Capability of Electrosprayed NiCo2O4 Nanoparticles as Li-ion Battery Anode”, Ionics, 2018.

2017

Journal Article

R. Panonnummal, Jayakumar, R., and Sabitha, M., “Comparative anti-psoriatic efficacy studies of clobetasol loaded chitin nanogel and marketed cream.”, Eur J Pharm Sci, vol. 96, pp. 193-206, 2017.[Abstract]


<p>In the present study chitin nanogel loaded with anti-psoriatic drug clobetasol was developed (CLCNG) for its topical delivery in psoriasis. CLCNG had the particle size of 132±14nm, with gel like consistency, stability in refrigerator, having higher drug release properties at acidic pH. CLCNG exhibited significant toxicity towards HaCaT and THP-1cell lines by MTT assay. The uptake of nanogel by HaCaT cell lines was confirmed by fluorescent microscopy. CLCNG at 0.35mg/ml exhibited significant anti-inflammatory activity with an average of 65% and 70% inhibition in COX and LOX activities expressed in THP-1 cells. In vitro skin permeation studies revealed the increased transdermal flux with fragmented stratum corneum and loosened epidermal layers in CLCNG treated samples, compared with control drug solution. The in vivo anti-psoriatic studies done on imiquimod model confirmed the potential benefits of the nanogel for the topical delivery of clobetasol in psoriasis.</p>

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2017

Journal Article

S. Renuka Suseelan, Sreenivasan, S. Kaniyampad, Nair, S. Vasudevan, and Lakshmanan, V. - K., “Assessment of Poly (vinyl alcohol) Coated Flutamide Nanoparticulates and their Efficacy on Prostate Cancer Cells.”, Curr Drug Deliv, vol. 14, no. 5, pp. 641-649, 2017.[Abstract]


<p><b>BACKGROUND: </b>Flutamide (FLT) is a non steroidal antiandrogenic drug used to treat prostate cancer. Its poor aqueous solubility and toxicity are the major hindrance for oral drug delivery. The aims of this study are to introduce nanoformulation of flutamide to increase its aqueous solubility thereby improves the therapeutic efficacy of the chemodrug.</p><p><b>METHODS: </b>Poly (vinyl alcohol) (PVA) coated flutamide nanoparticles (PVA FLT NPs) were formulated by nanoprecipitation method and characterized by DLS, TEM, FTIR, Drug release profile and biological assays.</p><p><b>RESULTS: </b>The PVA FLT nanoparticles were about 300nm size and spherical in shape. The PVA coated flutamide nanoparticles were monodispersed and polycrystalline. The FTIR spectra confirmed the encapsulation of flutamide in PVA FLT NPs. The encapsulation efficiency and loading efficiency was found to be about 78% and 15% respectively. The in vitro drug release of nanoparticles was calculated and it showed a sustained release up to 120 hrs at pH 7.4. The in vitro cytotoxicity, colony forming ability and blood compatibility were also investigated. The in vitro cytotoxicity study indicated the dose dependent cytotoxicity of PVA FLT NPs. In vitro clonogenic assay revealed that the PVA FLT NPs treated PC3 cells had less colony forming ability than the untreated PC3 cells. In vitro hemolysis assay and blood aggregation studies confirmed the hemocompatibility of the prepared PVA FLT NPs.</p><p><b>CONCLUSION: </b>We reported PVA coated FLT NPs were prepared by nanoprecipitation were more aqueous soluble than FLT, which increased its therapeutic efficacy for prostate cancer cells.</p>

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2017

Journal Article

A. Mohan, Nair, S. V., and Lakshmanan, V. - K., “Leucas aspera Nanomedicine Shows Superior Toxicity and Cell Migration Retarded in Prostate Cancer Cells.”, Appl Biochem Biotechnol, vol. 181, no. 4, pp. 1388-1400, 2017.[Abstract]


<p>Prostate cancer is one of the most common malignancies among men worldwide. The main aim of the present work was to clarify the advantages of a nanoformulation of ayurvedic herbal plants. Specifically, we assessed the improved anticancer activity of Leucas aspera nanoparticles compared with methanolic crude extract in PC3 prostate cancer cells and normal cells. L. aspera is a plant that is used in ayurveda due to the antirheumatic, antipyretic, anti-inflammatory, antibacterial, anticancer, and cytotoxic activities. Nanoparticles of L. aspera were prepared from plant methanolic extracts. Cytotoxic effect was studied in the normal and prostate cancer cells. Size and morphology of the formulated nanoparticles was assessed using dynamic light scattering and scanning electron microscopy. In vitro cytotoxicity of L. aspera nanoparticles for PC3 cells was concentration- and time-dependent. In vitro hemolysis assay, cellular uptake studies, cell aggregation studies, and cell migration assay established the anticancerous activity of L. aspera in prostate cancer.</p>

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2017

Journal Article

S. Sowmya, Mony, U., Jayachandran, P., Reshma, S., R Kumar, A., Arzate, H., Nair, S. V., and Jayakumar, R., “Tri-Layered Nanocomposite Hydrogel Scaffold for the Concurrent Regeneration of Cementum, Periodontal Ligament, and Alveolar Bone.”, Adv Healthc Mater, vol. 6, no. 7, 2017.[Abstract]


<p>A tri-layered scaffolding approach is adopted for the complete and concurrent regeneration of hard tissues-cementum and alveolar bone-and soft tissue-the periodontal ligament (PDL)-at a periodontal defect site. The porous tri-layered nanocomposite hydrogel scaffold is composed of chitin-poly(lactic-co-glycolic acid) (PLGA)/nanobioactive glass ceramic (nBGC)/cementum protein 1 as the cementum layer, chitin-PLGA/fibroblast growth factor 2 as the PDL layer, and chitin-PLGA/nBGC/platelet-rich plasma derived growth factors as the alveolar bone layer. The tri-layered nanocomposite hydrogel scaffold is cytocompatible and favored cementogenic, fibrogenic, and osteogenic differentiation of human dental follicle stem cells. In vivo, tri-layered nanocomposite hydrogel scaffold with/without growth factors is implanted into rabbit maxillary periodontal defects and compared with the controls at 1 and 3 months postoperatively. The tri-layered nanocomposite hydrogel scaffold with growth factors demonstrates complete defect closure and healing with new cancellous-like tissue formation on microcomputed tomography analysis. Histological and immunohistochemical analyses further confirm the formation of new cementum, fibrous PDL, and alveolar bone with well-defined bony trabeculae in comparison to the other three groups. In conclusion, the tri-layered nanocomposite hydrogel scaffold with growth factors can serve as an alternative regenerative approach to achieve simultaneous and complete periodontal regeneration.</p>

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2017

Journal Article

A. Anitha, Joseph, J., Menon, D., Nair, S. V., and Nair, M. B., “Electrospun Yarn Reinforced NanoHA Composite Matrix as a Potential Bone Substitute for Enhanced Regeneration of Segmental Defects.”, Tissue Eng Part A, vol. 23, no. 7-8, pp. 345-358, 2017.[Abstract]


<p>Nanohydroxyapatite (nanoHA) is a well-established synthetic bone substitute with excellent osteoconduction and osteointegration. However, brittleness coupled with slow degradation curtails its load-bearing and bone regeneration potential, respectively. To address these limitations, nanoHA composite matrix reinforced with electrospun fibrous yarns was fabricated and tested in vitro and in vivo. Different weight percentages (5, 10, 15 wt%) and varying lengths (short and continuous) of poly(l-lactic acid) yarns were randomly dispersed in a gelatinous matrix containing nanoHA. This significantly improved the compressive strength as well as work of fracture, especially for continuous yarns at high weight percentages (10 and 15 wt%). Incorporation of yarns did not adversely affect the pore size (50-350 μm) or porosity of the scaffolds as well as the in vitro cellular response. Finally, when tested in a critical-sized femoral segmental defect in rat, the nanocomposite scaffolds induced osteoblast cell infiltration at 2 months that subsequently underwent increased mature lamellar bone formation at 4 months, in both the mid and peripheral defect regions. Histomorphometric analysis demonstrated that new bone formation and biomaterial degradation were significantly enhanced in the composite scaffold when compared to commercially available HA. Overall, the composite matrix reinforced with electrospun yarns proved to be a potential bone substitute having an appropriate balance between mechanical strength, porosity, biodegradation, and bone regeneration ability.</p>

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2017

Journal Article

G. J. Pillai, Paul-Prasanth, B., Nair, S. V., and Menon, D., “Influence of surface passivation of 2-Methoxyestradiol loaded PLGA nanoparticles on cellular interactions, pharmacokinetics and tumour accumulation.”, Colloids Surf B Biointerfaces, vol. 150, pp. 242-249, 2017.[Abstract]


<p>In the present work, 2-Methoxyestradiol [2ME2] loaded PLGA nanoparticles [NPs] were stabilized with Casein or poly(ethylene glycol) [PEG] and evaluated for its cellular interactions, pharmacokinetics and tumour accumulation. Surface stabilized PLGA nanoparticles prepared through a modified emulsion route possessed similar size, surface charge, drug loading and release characteristics. Particle-cell interactions as well as the anti-angiogenesis activity were similar for both nanoformulations in vitro. However, in vivo pharmacokinetics and tumour accumulation of the drug were substantially improved for the PEGylated nanoformulation. Reduced protein binding was observed for PEG stabilized PLGA NPs. Thus, it was demonstrated that nanoencapsulation of 2-ME2 within PEGylated PLGA nanocarrier could improve its half-life and plasma concentration and thereby increase the tumour accumulation.</p>

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2017

Journal Article

A. K. Haridas, Gangaja, B., Srikrishnarka, P., Unni, G. E., A. Nair, S., Shantikumar V Nair, and Dr. Dhamodaran Santhanagopalan, “Spray pyrolysis-deposited nanoengineered TiO2 thick films for ultra-high areal and volumetric capacity lithium ion battery applications”, Journal of Power Sources, vol. 345, pp. 50 - 58, 2017.[Abstract]


Abstract Energy storage technologies are sensitively dependent on electrode film quality, thickness and process scalability. In Li-ion batteries, using additive-free titania (TiO2) as electrodes, we sought to show the potential of spray pyrolysis-deposited nanoengineered films with thicknesses up to 135 μm exhibiting ultra-high areal capacities. Detailed electron microscopic characterization indicated that the achieved thick films are composed of highly crystalline anatase TiO2 particles with sizes on the order of 10–12 nm and porous as well. A 135 μm thick film yielded ultra-high areal and volumetric capacities of 3.7 mAh cm−2 and 274 mAh cm−3, respectively, at 1C rate. Also the present work recorded high Coulombic efficiency and good cycling stability. The best previously achieved capacities for additive-free TiO2 films have been less than 0.25 mAh cm−2 and With additives, best reported areal capacity in the literature has been 2.5 mAh cm−2 at 1C rate, but only with electrode thickness as high as 1400 μm. Formation of through-the-thickness percolation of Ti3+ conductive network upon lithiation contributed substantially for the superior performance. Spray pyrolysis deposition of nanoparticulate TiO2 electrodes have the potential to yield volumetric capacities an order of magnitude higher than the other processes previously reported without sacrificing performance and process scalability. More »»

2017

Journal Article

P. Madhusudanan, Reade, S., and Dr. Sahadev Shankarappa, “Neuroglia as Targets for Drug Delivery Systems: A Review”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 13, pp. 667-679, 2017.[Abstract]


Targeted drug delivery within the nervous system is an emerging topic of research that involves designing and developing vehicular delivery systems that have the ability to target specific neuronal and non-neuronal cell types in the central and peripheral nervous system. Drugs, genetic material, or any other payloads can be loaded onto such delivery systems and could be used to treat, prevent or manage various neurological disorders. Currently, majority of studies in this field have been concentrated around targeted delivery to neurons. However, the non-neuronal cells within the nervous system, collectively called neuroglia, have been largely ignored, though it is well known that they play a significant role in the pathophysiology of almost all neurological disorders. In this review, we present current developments in the specific area of neuroglia targeted delivery systems and highlight the use of polymeric, metallic, liposomal and other delivery systems used for this purpose.

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2017

Journal Article

B. Gangaja, Chandrasekharan, S., Vadukumpully, S., Shantikumar V Nair, and Dr. Dhamodaran Santhanagopalan, “Surface chemical analysis of CuO nanofiber composite electrodes at different stages of lithiation/delithiation”, Journal of Power Sources, vol. 340, pp. 356 - 364, 2017.[Abstract]


Abstract High aspect ratio, electrospun CuO nanofibers have been fabricated and tested for its electrochemical performance as lithium ion battery anode. These nanofibers are composed of CuO nanoparticles about 35–40 nm in size forming good inter-connected network. Fabricated half cells maintained specific capacity of 310 mAh g−1 at 1C rate for 100 cycles and stabilized capacity of about 120 mAh g−1 at 5C rate for 1000 cycles. Ex situ x-ray photoelectron spectroscopy (XPS) was performed to understand the electrodes surface chemical changes at the end of first discharge, first charge and after tenth charge. The solid electrolyte interface (SEI) layer comprised of LiF, Li2CO3 and Li2O while their quantity varied depending on the stage of lithiation/delithiation. Initially, no copper signal is observed on the surface of the \{SEI\} layer. However, in situ sputtering of the electrodes in the \{XPS\} chamber revealed that at the end of first discharge, formation Cu0 with detectable fraction of LixCuO2 and hydroxide in the \{SEI\} layer. At the end of first charge, a large fraction of Cu2O phase with a small fraction of hydroxide is observed. At the end of 10th charge no change in \{SEI\} layer content but increase in thickness was observed. More »»

2017

Journal Article

S. P. Madhusudanan, Gangaja, B., Shyla, A. G., A. Nair, S., Shantikumar V Nair, and Dr. Dhamodaran Santhanagopalan, “Sustainable chemical synthesis for phosphorus-doping of TiO2 nanoparticles by upcycling human urine and impact of doping on energy applications”, ACS Sustainable Chem. Eng, pp. 2393–2399, 2017.[Abstract]


Recently, there has been significant research interest toward sustainable chemical synthesis and processing of nanomaterials. Human urine, a pollutant, requires energy intensive processing steps prior to releasing into rivers and oceans. Upcyling urine has been proposed and practiced as a sustainable process in the past. Doping is one of the foremost processes to elevate the functionality of nanomaterials depending on the applications it is sought for. Phosphorus doping in to TiO2 nanomaterials has been of research interest over a decade now, that has been chiefly done using acidic precursors. Here we demonstrate, upcycling urine, a sustainable process for phosphorus doping into TiO2 lattice. Upon doping the changes in morphology, surface chemistry and band gap is studied in detail and compared with undoped TiO2 that is prepared using deionized water instead of urine. X-ray photoelectron spectroscopy confirmed that the P was replacing Ti in the lattice and exists in P5+ state with a quantified concentration of 2.5–3 at %. P-doped nanoparticles were almost 50% smaller in size with a lower concentration of surface −OH groups and a band gap increase of 0.3 eV. Finally, impact of these changes on energy devices such as dye-sensitized solar cells and li-ion batteries has been investigated. It is confirmed that P-doping induced surface chemical and band gap changes in TiO2 affected the solar cell characteristics negatively, while the smaller particle size and possibly wider surface channels improved Li-ion battery performance. More »»

2017

Journal Article

J. John, Gangaja, B., Shantikumar V Nair, and Dr. Dhamodaran Santhanagopalan, “Conformal coating of TiO2 shell on silicon nanoparticles for improved electrochemical performance in Li-ion battery applications”, Electrochimica Acta, vol. 235, pp. 191 - 199, 2017.[Abstract]


Abstract A scalable wet chemical process for conformal TiO2 coating on silicon nanoparticles is investigated for Li-ion battery applications. The stable core-shell composite nanoparticles along with polyacrylic acid (PAA) binder was studied as an anode in Li-ion batteries and compared with bare-Si as a control. By limiting the charge capacity to 1500 mAh g−1, we established stable cycling (zero fade) for over 50 cycles for the core-shell compared to inferior stability (only 30% capacity retention) of the bare-Si nanoparticles at 0.1C rate. Stable capacity of 800 mAh g−1 at 1C rate over 100 cycles was also demonstrated for the core-shell nanoparticle electrode. Transmission electron microscopy and X-ray photoelectron spectroscopy characterizations indicate that in absence of TiO2 the solid electrolyte interface (SEI) layer which forms around Si was about 8–10 nm and composed of Li2O and LiF. In contrast, the \{SEI\} layer around the TiO2 shell has been thinner (about 2–3 nm) and composed of LiF and LixPFyOz, that stabilized the surface leading to improved cycling stability. Thinner \{SEI\} layer and its composition led to lower charge transfer resistance while the interface between the composite and the Cu-current collector has better adhesion compared to the bare-Si electrode. Impedance spectroscopy measurements confirmed the above. More »»

2017

Journal Article

S. Vijaykumar Patil and S Y Nanduri, L., “Interaction of chitin/chitosan with salivary and other epithelial cells-An overview.”, Int J Biol Macromol, vol. 104, no. Pt B, pp. 1398-1406, 2017.[Abstract]


<p>Chitin and its deacetylated form, chitosan, have been widely used for tissue engineering of both epithelial and mesenchymal tissues. Epithelial cells characterised by their sheet-like tight cellular arrangement and polarised nature, constitute a major component in various organs and play a variety of roles including protection, secretion and maintenance of tissue homeostasis. Regeneration of damaged epithelial tissues has been studied using biomaterials such as chitin, chitosan, hyaluronan, gelatin and alginate. Chitin and chitosan are known to promote proliferation of various embryonic and adult epithelial cells. However it is not clearly understood how this activity is achieved or what are the mechanisms involved in the chitin/chitosan driven proliferation of epithelial cells. Mechanistic understanding of influence of chitin/chitosan on epithelial cells will guide us to develop more targeted regenerative scaffold/hydrogel systems. Therefore, current review attempts to elicit a mechanistic insight into how chitin and chitosan interact with salivary, mammary, skin, nasal, lung, intestinal and bladder epithelial cells.</p>

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2017

Journal Article

P. S. Panicker, Melge, A. R., Biswas, L., Keechilat, P., and Mohan, C. G., “Epidermal growth factor receptor (EGFR) structure-based bioactive pharmacophore models for identifying next-generation inhibitors against clinically relevant EGFR mutations.”, Chem Biol Drug Des, vol. 90, no. 4, pp. 629-636, 2017.[Abstract]


<p>Present work elucidates identification of next generation inhibitors for clinically relevant mutations of epidermal growth factor receptor (EGFR) using structure-based bioactive pharmacophore modeling followed by virtual screening (VS) techniques. Three-dimensional (3D) pharmacophore models of EGFR and its different mutants were generated. This includes seven 3D pharmacophoric points with three different chemical features (descriptors), that is, one hydrogen bond donor, three hydrogen bond acceptors and three aromatic rings. Pharmacophore models were validated using decoy dataset, Receiver operating characteristic plot, and external dataset compounds. The robust, bioactive 3D e-pharmacophore models were then used for VS of four different small compound databases: FDA approved, investigational, anticancer, and bioactive compounds collections of Selleck Chemicals. CUDC101 a multitargeted kinase inhibitor showed highest binding free energy and 3D pharmacophore fit value than the well known EGFR inhibitors, Gefitinib and Erlotinib. Further, we obtained ML167 as the second best hit on VS from bioactive database showing high binding energy and pharmacophore fit value with respect to EGFR receptor and its mutants. Optimistically, presented drug discovery based on the computational study serves as a foundation in identifying and designing of more potent EGFR next-generation kinase inhibitors and warrants further experimental studies to fight against lung cancer.</p>

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2017

Journal Article

C. C. Mohan, Cherian, A. Mary, Kurup, S., Joseph, J., Nair, M. B., Vijayakumar, M., Nair, S. V., and Menon, D., “Stable Titania Nanostructures on Stainless Steel Coronary Stent Surface for Enhanced Corrosion Resistance and Endothelialization.”, Adv Healthc Mater, vol. 6, no. 11, 2017.[Abstract]


<p>Stainless steel (SS) coronary stents continue to present risk of in-stent restenosis that impact its long term safety and efficacy. The present work focuses on developing a drug-free and polymer-less surface on coronary stents by utilizing a titania (TiO ) nanotexturing approach through hydrothermal processing, that will offer improved stent performance in vivo. Mechanically stable and durable nanotextured coatings are obtained on SS stents that also offer good corrosion resistance. In vitro vascular cell (endothelial and smooth muscle cells) studies on surface modified SS show preferential rapid endothelialization with enhanced nitric oxide production and reduce smooth muscle cell proliferation, in comparison to unmodified SS. In vivo evaluation of the nanotextured stents after subcutaneous implantation in rabbits show reduced irritability and minimal localized inflammatory response. These beneficial effects suggest that the stable, easily scalable titania nanosurface modification strategy on coronary stent surfaces can be a much cheaper alternative to drug eluting stents in addressing in-stent restenosis.</p>

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2017

Journal Article

R. Ramachandran, Junnuthula, V. Reddy, G Gowd, S., Ashokan, A., Thomas, J., Peethambaran, R., Thomas, A., Unni, A. Kodakara K., Panikar, D., Nair, S. V., and Koyakutty, M., “Theranostic 3-Dimensional nano brain-implant for prolonged and localized treatment of recurrent glioma.”, Sci Rep, vol. 7, p. 43271, 2017.[Abstract]


<p>Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching. Orthotopic rat glioma implanted wafers showed constant drug release (116.6 μg/day) with negligible leakage into the peripheral blood (<100 ng) rendering ~1000 fold differential drug dosage in tumor versus peripheral blood. Most importantly, implant with one month release profile resulted in long-term (>4 month) survival of 85.7% animals whereas 07 day releasing implant showed tumor recurrence in 54.6% animals, rendering a median survival of only 74 days. In effect, we show that highly controlled drug delivery is possible for prolonged periods in orthotopic brain-tumor using combinatorial nanofibre libraries of bulk-eroding polymers, thereby controlling glioma recurrence.</p>

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2017

Journal Article

A. Mohandas, Krishnan, A. G., Dr. Raja Biswas, Dr. Deepthy Menon, and Dr. Manitha B. Nair, “Antibacterial and cytocompatible nanotextured Ti surface incorporating silver via single step hydrothermal processing”, Materials Science and Engineering C, vol. 75, pp. 115-124, 2017.[Abstract]


Nanosurface modification of Titanium (Ti) implants and prosthesis is proved to enhance osseointegration at the tissue–implant interface. However, many of these products lack adequate antibacterial capability, which leads to implant loosening. As a curative strategy, in this study, nanotextured Ti substrates embedded with silver nanoparticles were developed through a single step hydrothermal processing in an alkaline medium containing silver nitrate at different concentrations (15, 30 and 75 μM). Scanning electron micrographs revealed a non-periodically oriented nanoleafy structure on Ti (TNL) decorated with Ag nanoparticles (nanoAg), which was verified by XPS, XRD and EDS analysis. This TNLAg substrate proved to be mechanically stable upon nanoindentation and nanoscratch tests. Silver ions at detectable levels were released for a period of 28 days only from substrates incorporating higher nanoAg content. The samples demonstrated antibacterial activity towards both Escherichia coli and Staphylococcus aureus, with a more favorable response to the former. Simultaneously, Ti substrates incorporating nanoAg at all concentrations supported the viability, proliferation and osteogenic differentiation of mesenchymal stem cells. Overall, nanoAg incorporation into surface modified Ti via a simple one-step thermochemical method is a favorable strategy for producing implants with dual characteristics of antibacterial activity and cell compatibility. © 2017 Elsevier B.V.

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2017

Journal Article

Dr. Anil Kumar V., Sachu, A., Mohan, K., Vinod, V., Dinesh, K. Radhakrish, and Karim, S., “Simple low cost differentiation of Candida auris from Candida haemulonii complex using CHROMagar Candida medium supplemented with Pal's medium”, Revista Iberoamericana de Micologia, 2017.[Abstract]


Background: Candida auris is unique due to its multidrug resistance and misidentification as Candida haemulonii by commercial systems. Its correct identification is important to avoid inappropriate treatments. Aims: To develop a cheap method for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Methods: Fifteen C. auris isolates, six isolates each of C. haemulonii and Candida duobushaemulonii, and one isolate of Candida haemulonii var. vulnera were tested using CHROMagar Candida medium supplemented with Pal's agar for better differentiation. Results: On CHROMagar Candida medium supplemented with Pal's agar all C. auris strains showed confluent growth of white to cream colored smooth colonies at 37. °C and 42. °C after 24 and 48. h incubation and did not produce pseudohyphae. The isolates of the C. haemulonii complex, on the contrary, showed poor growth of smooth, light-pink colonies at 24. h while at 48. h the growth was semiconfluent with the production of pseudohyphae. C. haemulonii complex failed to grow at 42. °C. Conclusions: We report a rapid and cheap method using CHROMagar Candida medium supplemented with Pal's agar for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. © 2017 Asociación Española de Micología.

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2017

Journal Article

P. H. Domingues, S Y Nanduri, L., Seget, K., Venkateswaran, S. V., Agorku, D., Viganó, C., von Schubert, C., Nigg, E. A., Swanton, C., Sotillo, R., Bosio, A., Storchová, Z., and Hardt, O., “Cellular Prion Protein PrP and Ecto-5'-Nucleotidase Are Markers of the Cellular Stress Response to Aneuploidy.”, Cancer Res, vol. 77, no. 11, pp. 2914-2926, 2017.[Abstract]


<p>Aneuploidy is a hallmark of most human tumors, but the molecular physiology of aneuploid cells is not well characterized. In this study, we screened cell surface biomarkers of approximately 300 proteins by multiparameter flow cytometry using multiple aneuploid model systems such as cell lines, patient samples, and mouse models. Several new biomarkers were identified with altered expression in aneuploid cells, including overexpression of the cellular prion protein CD230/PrP and the immunosuppressive cell surface enzyme ecto-5'-nucleotidase CD73. Functional analyses associated these alterations with increased cellular stress. An increased number of CD73 cells was observed in confluent cultures in aneuploid cells relative to their diploid counterparts. An elevated expression in CD230/PrP was observed in serum-deprived cells in association with increased generation of reactive oxygen species. Overall, our work identified biomarkers of aneuploid karyotypes, which suggest insights into the underlying molecular physiology of aneuploid cells. .</p>

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2017

Journal Article

Y. A. Skorik, Golyshev, A. A., Kritchenkov, A. S., Gasilova, E. R., Poshina, D. N., Sivaram, A. J., and Jayakumar, R., “Development of drug delivery systems for taxanes using ionic gelation of carboxyacyl derivatives of chitosan.”, Carbohydr Polym, vol. 162, pp. 49-55, 2017.[Abstract]


<p>Nanoparticles of two chitosan derivatives - N-succinyl-chitosan (SC) and N-glutaryl-chitosan (GC) - were developed as passive transport systems for taxanes (paclitaxel and docetaxel) using an ionic gelation technique with sodium tripolyphosphate. These nanoparticles had an apparent hydrodynamic diameter of 300-350nm, a ζ-potential of 25-31mV, an encapsulation efficiency of 21-26%, and a drug loading efficiency of 6-13%. DLS and SLS analysis shows that the nanoparticles have a unimodal size distribution and spherical form. Drug release kinetics of the taxane-loaded nanoparticles demonstrates that more than 50% of the loaded taxane could be released upon the degradation of the nanoparticles after targeted delivery. The drug-loaded SC and GC nanoparticles exhibit high cytotoxicity towards AGS cancer cell lines and their antitumor activity is consequently enhanced when compared with free taxanes.</p>

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2017

Journal Article

D. S. Baji, Shantikumar V Nair, and Alok Kumar Rai, “Highly porous disk-like shape of Co3O4 as an anode material for lithium ion batteries”, Journal of Solid State Electrochemistry, pp. 1-7, 2017.[Abstract]


A novel disk-like shape of Co3O4 with high porosity was synthesized by a facile hydrothermal approach followed by calcination at 485 °C for 2 h. In order to further confirm the crystal structure, morphology, particle size, surface area, and porosity of the sample, a series of corresponding characterization techniques were used. The disk-like shape of Co3O4 as an anode delivered excellent rate capability such as 510.5 mAh g−1 at 4.0 C, which is much higher than the theoretical capacity of commercial graphite anode (372 mAh g−1). However, the electrode could not recover the high capacity during the long-term cycling at various higher current rates due to the deformation of the structure as confirmed by the ex situ studies. It is believed that the obtained remarkable structural feature with numerous void pores within the structure may be helpful for short-term cycling due to the large contact areas between the electrode and the electrolyte and a shorter diffusion length for lithium ion insertion but unable to act as a buffer to relax the volume expansion/contraction and alleviate the structural damage of the electrode during long-term cycling. © 2017 Springer-Verlag Berlin Heidelberg

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2017

Journal Article

P. Rajitha, Biswas, R., Sabitha, M., and Jayakumar, R., “Methotrexate in the Treatment of Psoriasis and Rheumatoid Arthritis: Mechanistic Insights, Current Issues and Novel Delivery Approaches.”, Curr Pharm Des, vol. 23, no. 24, pp. 3550-3566, 2017.[Abstract]


<p>Our review is focused on the use of methotrexate in drug therapy of two autoimmune diseases, psoriasis and rheumatoid arthritis (RA). The article describes the pathogenesis of psoriasis and RA, the role of methotrexate in the treatment of these diseases with more focused review on the mechanism behind the clinical benefits of methotrexate therapy. Methotrexate due to its cytotoxic, anti-inflammatory and immune modulatory activities provides clinical benefits in the therapy of the selected diseases. This review also gives a panorama of the problems associated with the use of methotrexate in the selected diseases and the guidelines provided by FDA for its safe use. The novel colloidal drug delivery systems of methotrexate, with particular emphasis on advantages offered by liposomal formulation, niosomal gel, hydrogel, albumin conjugates, nanoparticles and nano structured lipid carriers in psoriasis and RA are also reviewed. It seemed that the use of newer colloidal carriers with improved skin permeability by minimizing its systemic availability will be a useful strategy to reduce the toxic effects of the drug in psoriatic patients. In rheumatoid arthritis patients, the development of newer therapeutic strategies using appropriate targeting ligands that specifically deliver the drug to the inflamed joint space will help to overcome its toxic effects by minimizing the systemic exposure.</p>

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2017

Journal Article

J. Anjana, Rajan, V. K., Biswas, R., and Jayakumar, R., “Controlled Delivery of Bioactive Molecules for the Treatment of Chronic Wounds.”, Curr Pharm Des, vol. 23, no. 24, pp. 3529-3537, 2017.[Abstract]


<p>A cut or break on the surface of the skin is usually referred to as a wound. Any wound has a potential to heal by itself through a complex cascade of events. However, some wounds show delayed healing due to their underlying physiology and are referred to as chronic wounds like diabetic ulcers, venous ulcers, pressure ulcers and chronic infected ulcers. Extensive care has to be taken for the management of chronic wounds and these have become a major concern in the current medical scenario. The use of bioactive molecules or in other words the molecules that can actively interact with the wound environment and help in wound healing are gaining much importance. The incorporation of bioactive molecules into a suitable matrix system which not only provide a controlled release of the molecules, but also enable better exudate management is desired to overcome the shortcomings of the conventional treatment modalities. A major problem associated with chronic wounds is that they are easily prone to infections. In such cases, the topical delivery of antibiotics helps eliminate infection. However, the continuous use of high dose of antibiotics has led to the development of multi drug resistant bacterial strains. To overcome these issues, other broad-spectrum antimicrobial agents like antiseptics, metallic nanoparticles and antimicrobial peptides are being adopted nowadays. Growth factors play a major role in the wound healing cascade, thus topical delivery of growth factor from a suitable matrix is an interesting strategy. The delivery of nucleic acids with the aid of suitable vectors for either silencing a particular gene or over expressing a gene of interest is also being investigated nowadays. This review is an attempt to draw light over some of the recent approaches adopted for the treatment of chronic wounds using bioactive molecules like antibiotics, antiseptics, metallic nanoparticles or ions, growth factors and nucleic acids.</p>

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2017

Journal Article

T. Gonzalez-Fernandez, Sathy, B. N., Hobbs, C., Cunniffe, G. M., McCarthy, H. O., Dunne, N. J., Nicolosi, V., O'Brien, F. J., and Kelly, D. J., “Mesenchymal Stem Cell Fate Following Non-viral Gene Transfection Strongly Depends on the Choice of Delivery Vector”, Acta Biomaterialia, vol. 55, pp. 226-238, 2017.[Abstract]


Controlling the phenotype of mesenchymal stem cells (MSCs) through the delivery of regulatory genes is a promising strategy in tissue engineering (TE). Essential to effective gene delivery is the choice of gene carrier. Non-viral delivery vectors have been extensively used in TE, however their intrinsic effects on MSC differentiation remain poorly understood. The objective of this study was to investigate the influence of three different classes of non-viral gene delivery vectors: (1) cationic polymers (polyethylenimine, PEI), (2) inorganic nanoparticles (nanohydroxyapatite, nHA) and (3) amphipathic peptides (RALA peptide) on modulating stem cell fate after reporter and therapeutic gene delivery. Despite facilitating similar reporter gene transfection efficiencies, these nanoparticle-based vectors had dramatically different effects on MSC viability, cytoskeletal morphology and differentiation. After reporter gene delivery (pGFP or pLUC), the nHA and RALA vectors supported an elongated MSC morphology, actin stress fibre formation and the development of mature focal adhesions, while cells appeared rounded and less tense following PEI transfection. These changes in MSC morphology correlated with enhanced osteogenesis following nHA and RALA transfection and adipogenesis following PEI transfection. When therapeutic genes encoding for transforming growth factor beta 3 (TGF-β3) and/or bone morphogenic protein 2 (BMP2) were delivered to MSCs, nHA promoted osteogenesis in 2D culture and the development of an endochondral phenotype in 3D culture, while RALA was less osteogenic and appeared to promote a more stable hyaline cartilage-like phenotype. In contrast, PEI failed to induce robust osteogenesis or chondrogenesis of MSCs, despite effective therapeutic protein production. Taken together, these results demonstrate that the differentiation of MSCs through the application of non-viral gene delivery strategies depends not only on the gene delivered, but also on the gene carrier itself. Statement of Significance Nanoparticle-based non-viral gene delivery vectors have been extensively used in regenerative medicine, however their intrinsic effects on mesenchymal stem cell (MSC) differentiation remain poorly understood. This paper demonstrates that different classes of commonly used non-viral vectors are not inert and they have a strong effect on cell morphology, stress fiber formation and gene transcription in MSCs, which in turn modulates their capacity to differentiate towards osteogenic, adipogenic and chondrogenic lineages. These results also point to the need for careful and tissue-specific selection of nanoparticle-based delivery vectors to prevent undesired phenotypic changes and off-target effects when delivering therapeutic genes to damaged or diseased tissues. © 2017 Acta Materialia Inc.

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2017

Journal Article

A. A, Menon, D., B, S. T., Koyakutty, M., Mohan, C. C., Nair, S. V., and Dr. Manitha B. Nair, “Bioinspired Composite Matrix Containing Hydroxyapatite–Silica Core–Shell Nanorods for Bone Tissue Engineering”, ACS Applied Materials & Interfaces, vol. 9, no. 32, pp. 26707–26718, 2017.[Abstract]


Development of multifunctional bioinspired scaffolds that can stimulate vascularization and regeneration is necessary for the application in bone tissue engineering. Herein, we report a composite matrix containing hydroxyapatite (HA)–silica core–shell nanorods with good biocompatibility, osteogenic differentiation, vascularization, and bone regeneration potential. The biomaterial consists of a crystalline, rod-shaped nanoHA core with uniform amorphous silica sheath (Si–nHA) that retains the characteristic phases of the individual components, confirmed by high-resolution transmission electron microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The nanorods were blended with gelatinous matrix to develop as a porous, composite scaffold. The viability and functionality of osteogenically induced mesenchymal stem cells as well as endothelial cells have been significantly improved through the incorporation of Si–nHA within the matrix. Studies in the chicken chorioallantoic membrane and rat models demonstrated that the silica-containing scaffolds not only exhibit good biocompatibility, but also enhance vascularization in comparison to the matrix devoid of silica. Finally, when tested in a critical-sized femoral segmental defect in rats, the nanocomposite scaffolds enhanced new bone formation in par with the biomaterial degradation. In conclusion, the newly developed composite biomimetic scaffold may perform as a promising candidate for bone tissue engineering applications.

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2017

Journal Article

V. Selvaprithviraj, Sankar, D., Sivashanmugam, A., Srinivasan, S., and Jayakumar, R., “Pro-angiogenic Molecules for Therapeutic Angiogenesis.”, Curr Med Chem, vol. 24, no. 31, pp. 3413-3432, 2017.[Abstract]


<p><b>BACKGROUND: </b>Therapeutic angiogenesis is a clinical intervention for controlled stimulation and augmentation of neovascularisation in ischemic tissues. Conventional therapeutic techniques involve proangiogenic factor based induction of host tissue angiogenesis. In this review, we provide a holistic idea about therapeutic angiogenesis while specifically highlighting the role of proangiogenic factors as growth factors, peptides, small molecules and polysaccharides in tissue neovascularisation.</p><p><b>METHODS: </b>A detailed search of peer-reviewed literature was carried out with prime focus on therapeutic angiogenesis and proangiogenic factors. The content of each literature reviewed in this paper was qualitatively analysed for particulars and relevance to the subject of study. This work has been distributed under four broad titles, namely, proangiogenic growth factors, peptides, small molecules and polysaccharides. Also, recent developments pertaining to proangiogenic factors for therapeutic angiogenesis have been detailed.</p><p><b>RESULTS: </b>A total of 244 literatures have been reviewed from the bibliographic database to present a conceptual understanding about the importance of proangiogenic factors in revascularisation of ischemic tissues.</p><p><b>CONCLUSION: </b>This review focuses on importance of various proangiogenic factors, with reference to therapeutic angiogenesis. Thorough analysis of clinical data reveals the dearth of a defined system for proangiogenic growth factor delivery. Designing of a biomaterial based paradigm for growth factor therapy, might help in enhancing clinical translation of therapeutic angiogenesis.</p>

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2017

Journal Article

S. Pentlavalli, Chambers, P., Sathy, B. N., O'Doherty, M., Chalanqui, M., Kelly, D. J., Haut-Donahue, T., McCarthy, H. O., and Dunne, N. J., “Simple Radical Polymerization of Poly(Alginate-Graft-N-Isopropylacrylamide) Injectable Thermoresponsive Hydrogel with the Potential for Localized and Sustained Delivery of Stem Cells and Bioactive Molecules.”, Macromol Biosci, vol. 17, no. 11, 2017.[Abstract]


<p>In this study, thermoresponsive copolymers that are fully injectable, biocompatible, and biodegradable and are synthesized via graft copolymerization of poly(N-isopropylacrylamide) onto alginate using a free-radical reaction are presented. This new synthesis method does not involve multisteps or associated toxicity issues, and has the potential to reduce scale-up difficulties. Chemical and physical analyses verify the resultant graft copolymer structure. The lower critical solution temperature, which is a characteristic of sol-gel transition, is observed at 32 °C. The degradation properties indicate suitable degradation kinetics for drug delivery and bone tissue engineering applications. The synthesized P(Alg-g-NIPAAm) hydrogel is noncytotoxic with both human osteosarcoma (MG63) cells and porcine bone marrow derived mesenchymal stem cells (pBMSCs). pBMSCs encapsulated in the P(Alg-g-NIPAAm) hydrogel remain viable, show uniform distribution within the injected hydrogel, and undergo osteogenic and chondrogenic differentiation under appropriate culture conditions. Furthermore, for the first time, this work will explore the influence of alginate viscosity on the viscoelastic properties of the resulting copolymer hydrogels, which influences the rate of medical device formation and subsequent drug release. Together the results of this study indicate that the newly synthesized P(Alg-g-NIPAAm) hydrogel has potential to serve as a versatile and improved injectable platform for drug delivery and bone tissue engineering applications.</p>

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2017

Journal Article

S. Vijayrajratnam, Pushkaran, A. Choorakott, Balakrishnan, A., Vasudevan, A. Kumar, Biswas, R., and Mohan, C. Gopi, “Understanding the molecular differential recognition of muramyl peptide ligands by LRR domains of human NOD receptors.”, Biochem J, vol. 474, no. 16, pp. 2691-2711, 2017.[Abstract]


<p>Human nucleotide-binding oligomerization domain proteins, hNOD1 and hNOD2, are host intracellular receptors with C-terminal leucine-rich repeat (LRR) domains, which recognize specific bacterial peptidoglycan (PG) fragments as their ligands. The specificity of this recognition is dependent on the third amino acid of the stem peptide of the PG ligand, which is usually -diaminopimelic acid (DAP) or l-lysine (l-Lys). Since the LRR domains of hNOD receptors had been experimentally shown to confer the PG ligand-sensing specificity, we developed three-dimensional structures of hNOD1-LRR and the hNOD2-LRR to understand the mechanism of differential recognition of muramyl peptide ligands by hNOD receptors. The hNOD1-LRR and hNOD2-LRR receptor models exhibited right-handed curved solenoid shape. The hot-spot residues experimentally proved to be critical for ligand recognition were located in the concavity of the NOD-LRR and formed the recognition site. Our molecular docking analyses and molecular electrostatic potential mapping studies explain the activation of hNOD-LRRs, in response to effective molecular interactions of PG ligands at the recognition site; and conversely, the inability of certain PG ligands to activate hNOD-LRRs, by deviations from the recognition site. Based on molecular docking studies using PG ligands, we propose few residues - G825, D826 and N850 in hNOD1-LRR and L904, G905, W931, L932 and S933 in hNOD2-LRR, evolutionarily conserved across different host species, which may play a major role in ligand recognition. Thus, our integrated experimental and computational approach elucidates the molecular basis underlying the differential recognition of PG ligands by hNOD receptors.</p>

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2017

Journal Article

G. M. Cunniffe, Gonzalez-Fernandez, T., Daly, A., Sathy, B. N., Jeon, O., Alsberg, E., and Kelly, D. J., “ Three-Dimensional Bioprinting of Polycaprolactone Reinforced Gene Activated Bioinks for Bone Tissue Engineering.”, Tissue Eng Part A, vol. 23, no. 17-18, pp. 891-900, 2017.[Abstract]


<p>Regeneration of complex bone defects remains a significant clinical challenge. Multi-tool biofabrication has permitted the combination of various biomaterials to create multifaceted composites with tailorable mechanical properties and spatially controlled biological function. In this study we sought to use bioprinting to engineer nonviral gene activated constructs reinforced by polymeric micro-filaments. A gene activated bioink was developed using RGD-γ-irradiated alginate and nano-hydroxyapatite (nHA) complexed to plasmid DNA (pDNA). This ink was combined with bone marrow-derived mesenchymal stem cells (MSCs) and then co-printed with a polycaprolactone supporting mesh to provide mechanical stability to the construct. Reporter genes were first used to demonstrate successful cell transfection using this system, with sustained expression of the transgene detected over 14 days postbioprinting. Delivery of a combination of therapeutic genes encoding for bone morphogenic protein and transforming growth factor promoted robust osteogenesis of encapsulated MSCs in vitro, with enhanced levels of matrix deposition and mineralization observed following the incorporation of therapeutic pDNA. Gene activated MSC-laden constructs were then implanted subcutaneously, directly postfabrication, and were found to support superior levels of vascularization and mineralization compared to cell-free controls. These results validate the use of a gene activated bioink to impart biological functionality to three-dimensional bioprinted constructs.</p>

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2017

Journal Article

S. Fazal, Paul-Prasanth, B., Nair, S. V., and Menon, D., “Theranostic Iron Oxide/Gold Ion Nanoprobes for MR Imaging and Noninvasive RF Hyperthermia.”, ACS Appl Mater Interfaces, vol. 9, no. 34, pp. 28260-28272, 2017.[Abstract]


<p>This work focuses on the development of a nanoparticulate system that can be used for magnetic resonance (MR) imaging and E-field noninvasive radiofrequency (RF) hyperthermia. For this purpose, an amine-functional gold ion complex (GIC), [Au(III)(diethylenetriamine)Cl]Cl, which generates heat upon RF exposure, was conjugated to carboxyl-functional poly(acrylic acid)-capped iron-oxide nanoparticles (IO-PAA NPs) to form IO-GIC NPs of size ∼100 nm. The multimodal superparamagnetic IO-GIC NPs produced T2-contrast on MR imaging and unlike IO-PAA NPs generated heat on RF exposure. The RF heating response of IO-GIC NPs was found to be dependent on the RF power, exposure period, and particle concentration. IO-GIC NPs at a concentration of 2.5 mg/mL showed a high heating response (δT) of ∼40 °C when exposed to 100 W RF power for 1 min. In vitro cytotoxicity measurements on NIH-3T3 fibroblast cells and 4T1 cancer cells showed that IO-GIC NPs are cytocompatible at high NP concentrations for up to 72 h. Upon in vitro RF exposure (100 W, 1 min), a high thermal response leads to cell death of 4T1 cancer cells incubated with IO-GIC NPs (1 mg/mL). Hematoxylin and eosin imaging of rat liver tissues injected with 100 μL of 2.5 mg/mL IO-GIC NPs and exposed to low RF power of 20 W for 10 min showed significant loss of tissue morphology at the site of injection, as against RF-exposed or nanoparticle-injected controls. In vivo MR imaging and noninvasive RF exposure of 4T1-tumor-bearing mice after IO-GIC NP administration showed T2 contrast enhancement and a localized generation of high temperatures in tumors, leading to tumor tissue damage. Furthermore, the administration of IO-GIC NPs followed by RF exposure showed no adverse acute toxicity effects in vivo. Thus, IO-GIC NPs show good promise as a theranostic agent for magnetic resonance imaging and noninvasive RF hyperthermia for cancer.</p>

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2017

Journal Article

M. Saravanan, Shantikumar V Nair, and Rai, A. K., “Low Temperature Synthesis of Carbon-wrapped CuO Synthesized Without using a Conventional Carbon Source for Li ion Battery Application”, Physica E: Low-Dimensional Systems and Nanostructures, vol. 94, pp. 113-117, 2017.[Abstract]


Carbon-wrapped CuO is synthesized by a facile pyro-synthesis method without using a conventional carbon source to overcome the capacity fading issue of CuO nanoparticles. The microstructure analysis shows that the sample is fully wrapped by a carbon layer. The resultant carbon-wrapped CuO nanocomposite as an anode exhibits high reversible capacity with excellent cycling stability (437.1&nbsp;mAh/g at 0.25&nbsp;C and 365.2&nbsp;mAh/g at 1.0&nbsp;C after 100 cycles) and good rate capability. It is believed that the synergistic effect of CuO and carbon is responsible for the enhanced electrochemical performance of the nanocomposite electrode.

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2017

Journal Article

A. Raju, Shantikumar V Nair, and Lakshmanan, V. - K., “Biophytum Sensitivum Nanomedicine Reduces Cell Viability and Nitrite Production in Prostate Cancer Cells”, IET Nanobiotechnology, vol. 11, pp. 782-789, 2017.[Abstract]


Phytomedicine research received tremendous attention for novel therapeutic agent due to their safety and low cost. We assessed a novel nanoformulation of Biophytum sensitivum (BS), natural flavonoids for their improved efficacy and superior bioavailability against crude extract for prostate cancer cells (PC3). We prepared a nanomedicine of BS by nanoprecipitation method and size analysis via DLS and SEM revealed a range of 100-118 nm and surface zeta potential as -9.77 mV. FTIR was performed to evaluate functional for presence of carbonyl and aromatic rings, respectively. Human PC3 cells showed concentration at 0.5, 0.8, and 1 mg/ml dependent cytotoxicity 22, 39, and 56% for 24 h, whereas 43, 41, and 67% for 48 h of BS nanomedicine compared with crude 11, 22, and 53% for 24 h and 38, 31, and 60% for 48 h, respectively. Haemocompatibility of BS nanomedicine at the concentration of 0.5, 0.8, and 1 mg/ml did not show blood aggregation. Cellular uptake was confirmed using rhodamine-conjugated BS nanomedicine for 48 h. Interestingly, BS nanomedicine 1 mg/ml decreases the nitrite productions in PC3 cells. Collectively, BS nanomedicine has the potential anti-cancer agents with biocompatible and enhanced efficacy can be beneficial for the treatment of prostate cancer. © The Institution of Engineering and Technology 2017.

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2017

Journal Article

M. Chatterjee, D'Morris, S., Paul, V., Warrier, S., Vasudevan, A. Kumar, Vanuopadath, M., Nair, S. Sadasivan, Paul-Prasanth, B., C Mohan, G., and Biswas, R., “Mechanistic understanding of Phenyllactic acid mediated inhibition of quorum sensing and biofilm development in Pseudomonas aeruginosa.”, Appl Microbiol Biotechnol, vol. 101, no. 22, pp. 8223-8236, 2017.[Abstract]


<p>Pseudomonas aeruginosa depends on its quorum sensing (QS) system for its virulence factors' production and biofilm formation. Biofilms of P. aeruginosa on the surface of indwelling catheters are often resistant to antibiotic therapy. Alternative approaches that employ QS inhibitors alone or in combination with antibiotics are being developed to tackle P. aeruginosa infections. Here, we have studied the mechanism of action of 3-Phenyllactic acid (PLA), a QS inhibitory compound produced by Lactobacillus species, against P. aeruginosa PAO1. Our study revealed that PLA inhibited the expression of virulence factors such as pyocyanin, protease, and rhamnolipids that are involved in the biofilm formation of P. aeruginosa PAO1. Swarming motility, another important criterion for biofilm formation of P. aeruginosa PAO1, was also inhibited by PLA. Gene expression, mass spectrometric, functional complementation assays, and in silico data indicated that the quorum quenching and biofilm inhibitory activities of PLA are attributed to its ability to interact with P. aeruginosa QS receptors. PLA antagonistically binds to QS receptors RhlR and PqsR with a higher affinity than its cognate ligands N-butyryl-L-homoserine lactone (C-HSL) and 2-heptyl-3,4-dihydroxyquinoline (PQS; Pseudomonas quinolone signal). Using an in vivo intraperitoneal catheter-associated medaka fish infection model, we proved that PLA inhibited the initial attachment of P. aeruginosa PAO1 on implanted catheter tubes. Our in vitro and in vivo results revealed the potential of PLA as anti-biofilm compound against P. aeruginosa.</p>

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2017

Journal Article

N. K. Gayathri, Aparna, V., Maya, S., Biswas, R., Jayakumar, R., and C Mohan, G., “Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.”, Carbohydr Polym, vol. 177, pp. 67-76, 2017.[Abstract]


<p>We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery.</p>

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2017

Journal Article

E. S, R, N. T., K, R. V., Baranwal, G., Biswas, R., R, J., and S, S., “Fucoidan coated ciprofloxacin loaded chitosan nanoparticles for the treatment of intracellular and biofilm infections of Salmonella.”, Colloids Surf B Biointerfaces, vol. 160, pp. 40-47, 2017.[Abstract]


<p>Salmonella infections and their gallstone associated biofilm infections are difficult to treat due to poor penetration of antibiotics into the intracellular compartments of macrophages and within biofilms. Here we developed ciprofloxacin loaded chitosan nanoparticles (cCNPs) and fucoidan (Fu) coated cCNPs (Fu-cCNPs). Characterizations of these nanoparticles were carried out using Dynamic Light Scattering‎, Transmission electron microscopy and Fourier transform infrared spectroscopy. The prepared cCNPs and Fu-cCNPs have the size range of 124±7nm and 320±18nm, respectively. Both nanoparticles were found to be non-hemolytic and cytocompatible. In vitro sustained release of ciprofloxacin was observed from both cCNPs and Fu-cCNPs over a period of 2 weeks. The antimicrobial activity of cCNPs and Fu-cCNPs was tested under in vitro and in vivo conditions. The intracellular anti-Salmonella activity of Fu-cCNPs was 2 fold higher than cCNPs and 6 fold higher than ciprofloxacin alone. Fluorescence microscopic images confirmed enhanced delivery of Fu-cCNPs than the cCNPs within the intracellular compartment of macrophages. Both cCNPs and Fu-cCNPs are found to be equally effective in dispersing Salmonella Paratyphi A gallstone biofilms. The in vivo antibacterial activities of Fu-cCNPs were superior to cCNPs which we have validated using Salmonella Paratyphi A infected Drosophila melanogaster fly model. Our overall results showed that (1) Fu-cCNPs are more effective in eradicating Salmonella infections than cCNPs; (2) both cCNPs and Fu-cCNPs were equally effective in dispersing Salmonella gallstone biofilms.</p>

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2017

Journal Article

S. Pillarisetti, Maya, S., Sathianarayanan, S., and Jayakumar, R., “Tunable pH and redox-responsive drug release from curcumin conjugated γ-polyglutamic acid nanoparticles in cancer microenvironment.”, Colloids Surf B Biointerfaces, vol. 159, pp. 809-819, 2017.[Abstract]


<p>Tunable pH and redox responsive polymer was prepared using γ-polyglutamic acid (γ-PGA) with linker 3-mercaptopropionic acid (3-MPA) (γ-PGA_SH) via oxidation to obtain redox responsive disulfide (γ-PGA_SS) backbone and adipic acid dihydrazide (ADH) (γ-PGA_SS_ADH) with hydrazide functional group for pH responsiveness. Further curcumin (Cur) was conjugated through hydrazone bond of the γ-PGA_SS_ADH via Schiff base reaction to obtain (γ-PGA_SS_ADH_Cur). The prepared systems were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Qq-TOF-MS/MS) and Solid state nuclear magnetic resonance (SS NMR) techniques. γ-PGA_SS_ADH_Cur formed self-assembled core shell nanoparticles (NPs) in existence of stabilized aqueous medium. γ-PGA_SS_ADH_Cur NPs maintained its stability in physiological condition. NPs tunable Cur release and cytotoxicity were observed for γ-PGA_SS_ADH_Cur NPs in both acidic and redox conditions mimicking the cancer microenvironment. γ-PGA_SS_ADH_Cur NPs uptake study showed via endocytosis mechanism resulted in the lysosomal entrapment of these NPs within the cell. γ-PGA_SS_ADH_Cur NPs exhibited a dual stimuli responsive drug delivery and can be used as a smart and potential drug delivery system in cancer microenvironment.</p>

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2017

Journal Article

Dr. Jayakumar Rangasamy and Meenakshi, S., “Special Issue: 11th APCCS-2016-Chemistry, Environmental, Biotechnology and Biomedical Aspects of Chitin and Chitosan.”, Int J Biol Macromol, vol. 104, no. Pt B, p. 1371, 2017.

2017

Journal Article

S. M, S, U., Dr. Gopi Mohan C., B, S., IK, P., and R, J., “In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts.”, International Journal of Nanomedicine, 2017.[Abstract]


Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28-based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.

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2017

Journal Article

H. D. Kim, Amirthalingam, S., Kim, S. L., Lee, S. S., Rangasamy, J., and Hwang, N. S., “Biomimetic Materials and Fabrication Approaches for Bone Tissue Engineering.”, Adv Healthc Mater, vol. 6, no. 23, 2017.[Abstract]


<p>Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed.</p>

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2017

Journal Article

A. Sivashanmugam, Charoenlarp, P., Deepthi, S., Rajendran, A., Nair, S. V., Iseki, S., and Jayakumar, R., “Injectable Shear-Thinning CaSO/FGF-18-Incorporated Chitin-PLGA Hydrogel Enhances Bone Regeneration in Mice Cranial Bone Defect Model.”, ACS Appl Mater Interfaces, vol. 9, no. 49, pp. 42639-42652, 2017.[Abstract]


<p>For craniofacial bone regeneration, shear-thinning injectable hydrogels are favored over conventional scaffolds because of their improved defect margin adaptability, easier handling, and ability to be injected manually into deeper tissues. The most accepted method, after autografting, is the use of recombinant human bone morphogenetic protein-2 (BMP-2); however, complications such as interindividual variations, edema, and poor cost-efficiency in supraphysiological doses have been reported. The endogenous synthesis of BMP-2 is desirable, and a molecule which induces this is fibroblast growth factor-18 (FGF-18) because it can upregulate the BMP-2 expression  by supressing noggin. We developed a chitin-poly(lactide-co-glycolide) (PLGA) composite hydrogel by regeneration chemistry and then incorporated CaSO and FGF-18 for this purpose. Rheologically, a 7-fold increase in the elastic modulus was observed in the CaSO-incorporated chitin-PLGA hydrogels as compared to the chitin-PLGA hydrogel. Shear-thinning Herschel-Bulkley fluid nature was observed for both hydrogels. Chitin-PLGA/CaSO gel showed sustained release of FGF-18. In vitro osteogenic differentiation showed an enhanced alkaline phosphatase (ALP) expression in the FGF-18-containing chitin-PLGA/CaSO gel when compared to cells alone. Further, it was confirmed by studying the expression of osteogenic genes [RUNX2, ALP, BMP-2, osteocalcin (OCN), and osteopontin (OPN)], immunofluorescence staining of BMP-2, OCN, and OPN, and alizarin red S staining. Incorporation of FGF-18 in the hydrogel increased the endothelial cell migration. Further, the regeneration potential of the prepared hydrogels was tested in vivo, and longitudinal live animal μ-CT was performed. FGF-18-loaded chitin-PLGA/CaSO showed early and almost complete bone healing in comparison with chitin-PLGA/CaSO, chitin-PLGA/FGF-18, chitin-PLGA, and sham control systems, as confirmed by hematoxylin and eosin and osteoid tetrachrome stainings. This shows that the CaSO and FGF-18-incorporated hydrogel is a potential candidate for craniofacial bone defect regeneration.</p>

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2017

Journal Article

A. Ashokan, Somasundaram, V. Harish, Gowd, G. Siddaraman, Anna, I. M., Malarvizhi, G. L., Sridharan, B., Jobanputra, R. B., Peethambaran, R., Unni, A. K. K., Nair, S., and Koyakutty, M., “Biomineral Nano-Theranostic agent for Magnetic Resonance Image Guided, Augmented Radiofrequency Ablation of Liver Tumor.”, Sci Rep, vol. 7, no. 1, p. 14481, 2017.[Abstract]


<p>Theranostic nanoparticles based on biocompatible mineral compositions can significantly improve the translational potential of image guided cancer nano-therapy. Here, we report development of a single-phase calcium phosphate biomineral nanoparticle (nCP) with dual-mode magnetic resonance contrast (T1-T2) together with radiofrequency (RF) mediated thermal response suitable for image-guided RF ablation of cancer. The nanoparticles (NP) are engineered to provide dual MR contrast by an optimized doping concentration (4.1 at%) of paramagnetic ion, Fe, which also renders lossy dielectric character for nCP leading to thermal response under RF exposure. In vivo compatibility and dual-mode MR contrast are demonstrated in healthy rat models. MRI and T2 mapping suggest hepatobiliary clearance by ~96 hours. MRI guided intratumoral injection in subcutaneous rat glioma and orthotopic liver tumor models provide clear visualization of NP in MRI which also helps in quantifying NP distribution within tumor. Furthermore, by utilising RF mediated thermal response, NP treated tumor could be ablated using clinically approved RF ablation system (10 W,13.3 GHz). Real-time in vivo thermal imaging exhibits 119 ± 10% increase in temperature change (ΔT) for NP treated orthotopic liver tumor (ΔT = 51.5 ± 2 °C), compared to untreated healthy liver control (ΔT = 21.5 ± 2 °C). In effect, we demonstrate a promising nano-biomineral theranostic agent for dual-mode MRI combined with radiofrequency ablation of solid tumors.</p>

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2017

Journal Article

A. Jayasree, Mohandas, A., Seethalakshmy, S., Suresh, M., Riju R. Menon, Biswas, R., and Jayakumar, R., “Bi-layered nanocomposite bandages for controlling microbial infections and overproduction of matrix metalloproteinase activity”, International Journal of Biological Macromolecules, vol. 110, 2017.[Abstract]


Chronic diabetic wounds is characterised by increased microbial contamination and overproduction of matrix metalloproteases that would degrade the extracellular matrix. A bi-layer bandage was developed, that promotes the inhibition of microbial infections and matrix metalloprotease (MMPs) activity. Bi-layer bandage containing benzalkonium chloride loaded gelatin nanoparticles (BZK GNPs) in chitosan-Hyaluronic acid (HA) as a bottom layer and sodium alendronate containing chitosan as top layer was developed. We hypothesized that the chitosan-gelatin top layer with sodium alendronate could inhibit the MMPs activity, whereas the chitosan-HA bottom layer with BZK GNPs (240 ± 66 nm) would enable the elimination of microbes. The porosity, swelling and degradation nature of the prepared Bi-layered bandage was studied. The bottom layer could degrade within 4 days whereas the top layer remained upto 7 days. The antimicrobial activity of the BZK NPs loaded bandage was determined using normal and clinical strains. Gelatin zymography shows that the proteolytic activity of MMP was inhibited by the bandage.

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2017

Journal Article

T. S. Saranya, Rajan, V. K., Dr. Raja Biswas, Jayakumar, R., and Sathianarayanan, S., “Synthesis, Characterisation and Biomedical Applications of Curcumin Conjugated Chitosan Microspheres”, International Journal of Biological Macromolecules, 2017.[Abstract]


Curcumin is a diaryl heptanoid of curcuminoids class obtained from Curcuma longa. It possesses various biological activities like anti-inflammatory, hypoglycemic, antioxidant, wound-healing, and antimicrobial activities. Chitosan is a biocompatible, biodegradable and non-toxic natural polymer which enhances the adhesive property of the skin. Chemical conjugation will leads to sustained release action and to enhance the bioavailability. This study aims to synthesis and characterize biocompatible curcumin conjugated chitosan microspheres for bio-medical applications. The Schiff base reaction was carried out for the preparation of curcumin conjugated chitosan by microwave method and it was characterised using FTIR and NMR. Curcumin conjugated chitosan microspheres (CCCMs) were prepared by wet milling solvent evaporation method. SEM analysis showed these CCCMs were 2-5μm spherical particles. The antibacterial activities of the prepared CCCMs were studied against Staphylococcus aureus and Escherichia coli, the zone of inhibition was 28mm and 23mm respectively. Antioxidant activity of the prepared CCCMs was also studied by DPPH and H2O2 method it showed IC50 esteem value of 216μg/ml and 228μg/ml, and anti-inflammatory activity results showed that CCCMs having IC50 value of 45μg/ml. The results conclude that the CCCMs having a good antibacterial, antioxidant and anti-inflammatory activities. This, the prepared CCCMs have potential application in preventing skin infections.

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2017

Journal Article

A. Radhakrishnan, Gangaja, B., Nair, S., and Dr. Dhamodaran Santhanagopalan, “Reversible Cu4O3 Phase Formation in CuO Nanoplate Anodes for High Capacity and High Coulombic Efficiency”, ChemistrySelect, vol. 2, pp. 11548-11551, 2017.[Abstract]


Conversion materials with high specific capacity are of interest to improve energy density of Li-ion batteries. Here, we present results concerning hydrothermally synthesized CuO nanoplates that exhibit high specific capacity of 800 and 698 mAh/g at C/2 and 1C rates respectively and 180 mAh/g at a high rate of 30C. The electrodes exhibit high Coulombic efficiencies of about 66% and 60% at C/2 and 1C rate respectively, these are high efficiency values compared to the ones reported in the literature at respective rates. To understand the high performance, ex situ x-ray diffraction at different states of first discharge/charge is utilized that shine light on the lithiation/delithiation pathways of the CuO nanoplates. Lithiation proceeds through multiple phase transition CuO → Cu4O3 → Cu2O → Cu and it was found that Cu4O3 is reversible at the end of first charge. Cu and residual Cu2O was observed at the end of lithiation along with Li2O and Li2O2 phases. At the end of first charge, Cu4O3 phase along with CuO was observed as a major end-product with relatively minor concentrations of Cu2O. Cu4O3 as a major constituent observed in composite electrode seems to be the key information that can explain good reversibility and high Coulombic efficiency reported in the present work. © 2017 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

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2017

Journal Article

A. Ashok, Vijayaraghavan, S. N., Nair, S. V., and Dr. Mariyappan Shanmugam, “Molybdenum Trioxide Thin Film Recombination Barrier Layers for Dye Sensitized Solar Cells”, RSC Advances , 2017.[Abstract]


A physical vapor deposition based molybdenum trioxide (MoO3) thin film is demonstrated as an efficient reverse-electron recombination barrier layer (RBL) at the fluorine doped tin oxide (FTO)/titanium dioxide (TiO2) interface in dye sensitized solar cells (DSSCs). Thin films of MoO3 show an average optical transmittance of ∼77% in a spectral range of 350–800 nm with bandgap value of ∼3.1 eV. For an optimum thickness of MoO3, deposited for 5 minutes, the resulting DSSCs showed 15% enhancement in efficiency (η) compared to the reference DSSC which did not use MoO3 RBL; this suggests that MoO3 is effectively suppressing interfacial recombination at the FTO/TiO2 interface. Further, increasing the thickness of MoO3 RBL at the FTO/TiO2 interface (20 minutes deposition) is observed to impede charge transport, as noticed with 55% reduction in η compared to the reference DSSC. Thin film MoO3 RBL with an optimum thickness value at the FTO/TiO2 interface efficiently blocks the leaky transport pathways in the mesoporous TiO2 nanoparticle layer and facilitates efficient charge transport as confirmed by electrochemical impedance spectroscopy.

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2017

Journal Article

Dr. Bindhu Paul, Nair, R., Victor, A. C., and Paul-Prasanth, B., “Effects of N-Nitrosodiethylamine, a Potent Carcinogen, on Sexual Development, Gametogenesis, and Oocyte Maturation”, Sexual Development, vol. 11, no. 3, pp. 161-167, 2017.[Abstract]


N-Nitrosodiethylamine (DEN), a well-known hepatocarcinogen, is found in certain food products as such or as a metabolic byproduct. This study investigated the effects of DEN on sexual development, gametogenesis, and oocyte maturation in Japanese medaka (Oryzias latipes). DEN reduced the germ cell number dose-dependently during early stages of sexual differentiation in XX larvae, resulting in underdeveloped ovaries in adulthood at low doses. This effect was sex-specific as no such changes were seen in XY larvae. Furthermore, XX and XY larvae that were exposed at a low dose during early life showed a significant reduction in body weight in adulthood. Gonads in sexually immature adult medaka males and females exposed to DEN were in advanced stages in comparison to that of the controls. Gonado-somatic indices were significantly high in treated males and females. DEN induced oocyte maturation in vitro, which was inhibited by cordycepin, demonstrating that it stimulated oocyte maturation through polyadenylation of cyclin B mRNA as in the case of the endogenous maturation-inducing hormone. Altogether, our results have proven that DEN could disrupt or mimic the signaling pathways involved in germ cell development, proliferation, and maturation.

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2017

Journal Article

Dr. Lalitha Biswas, S, I., M, S., P, K., J, M., R, J., R, R., A, W., ,, SM, C. Mali, V, V., A, C., S, D., A, O., G, K., R, N., A, M., Z, P., and M, E., “First Two Bilateral Hand Transplantations in India (Part 4): Immediate Post-operative Care, Immunosuppression Protocol and Monitoring”, Indian J Plast Surg, vol. 50, no. 2, pp. 168-172, 2017.[Abstract]


Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'.

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2017

Journal Article

G. Baranwal, Mohammad, M., Jarneborn, A., Reddy, B. Raghunath, Golla, A., Chakravarty, S., Dr. Lalitha Biswas, Götz, F., Shankarappa, S., Jin, T., and Raja Biswas, “Impact of Cell Wall Peptidoglycan O-acetylation on the Pathogenesis of Staphylococcus Aureus in Septic Arthritis”, International Journal of Medical Microbiology, vol. 307, pp. 388 - 397, 2017.[Abstract]


Staphylococcus aureus (S. aureus) is one of the most common pathogen causing septic arthritis. To colonize the joints and establish septic arthritis this bacterium needs to resist the host innate immune responses. Lysozyme secreted by neutrophils and macrophages is an important defense protein present in the joint synovial fluids. S. aureus is known to be resistant to lysozyme due to its peptidoglycan modification by O-acetylation of N-acetyl muramic acid. In this study we have investigated the role of O-acetylated peptidoglycan in septic arthritis. Using mouse models for both local and hematogenous S. aureus arthritis we compared the onset and progress of the disease induced by O-acetyl transferase mutant and the parenteral wild type SA113 strain. The disease progression was assessed by observing the clinical parameters including body weight, arthritis, and functionality of the affected limbs. Further X-ray and histopathological examinations were performed to monitor the synovitis and bone damage. In local S. aureus arthritis model, mice inoculated with the ΔoatA strain developed milder disease (in terms of knee swelling, motor and movement functionality) compared to mice inoculated with the wild type SA113 strain. X-ray and histopathological data revealed that ΔoatA infected mice knee joints had significantly lesser joint destruction, which was accompanied by reduced bacterial load in knee joints. Similarly, in hematogenous S. aureus arthritis model, ΔoatA mutant strain induced significantly less severe clinical septic arthritis compared to its parental strain, which is in accordance with radiological findings. Our data indicate that peptidoglycan O-acetylation plays an important role in S. aureus mediated septic arthritis.

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2017

Journal Article

Dr. Lalitha Biswas, CG, N., M, B., Pradeep Jacob, Riju R. Menon, AK, R., and K, N., “Lack of Association of B-type Raf Kinase V600E Mutation with High-risk Tumor Features and Adverse Outcome in Conventional and Follicular Variants of Papillary Thyroid Carcinoma”, Indian Journal of Endocrinol Metab, vol. 21, no. 2, pp. 329-333, 2017.[Abstract]


INTRODUCTION:
Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome.

STUDY DESIGN:
Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue.

RESULTS:
Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome.

CONCLUSION:
BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.

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2017

Journal Article

P. S. Panicker, Melge, A. R., Dr. Lalitha Biswas, Keechilat, P., and Mohan, C. G., “Epidermal Growth Factor Receptor (EGFR) Structure-based Bioactive Pharmacophore Models for Identifying Next-generation Inhibitors Against Clinically relevant EGFR Mutations”, Chemical Biology & Drug Design, vol. 90, pp. 629-636, 2017.[Abstract]


Present work elucidates identification of next generation inhibitors for clinically relevant mutations of epidermal growth factor receptor (EGFR) using structure-based bioactive pharmacophore modeling followed by virtual screening (VS) techniques. Three-dimensional (3D) pharmacophore models of EGFR and its different mutants were generated. This includes seven 3D pharmacophoric points with three different chemical features (descriptors), that is, one hydrogen bond donor, three hydrogen bond acceptors and three aromatic rings. Pharmacophore models were validated using decoy dataset, Receiver operating characteristic plot, and external dataset compounds. The robust, bioactive 3D e-pharmacophore models were then used for VS of four different small compound databases: FDA approved, investigational, anticancer, and bioactive compounds collections of Selleck Chemicals. CUDC101 a multitargeted kinase inhibitor showed highest binding free energy and 3D pharmacophore fit value than the well known EGFR inhibitors, Gefitinib and Erlotinib. Further, we obtained ML167 as the second best hit on VS from bioactive database showing high binding energy and pharmacophore fit value with respect to EGFR receptor and its mutants. Optimistically, presented drug discovery based on the computational study serves as a foundation in identifying and designing of more potent EGFR next-generation kinase inhibitors and warrants further experimental studies to fight against lung cancer.

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2017

Journal Article

E. S., T.R., N., V.K., R., Baranwal, G., Raja Biswas, Dr. Jayakumar Rangasamy, and S., S., “Fucoidan Coated Ciprofloxacin loaded Chitosan Nanoparticles for the Treatment of Intracellular and Biofilm Infections of Salmonella”, Colloids and Surfaces B: Biointerfaces, vol. 160, pp. 40 - 47, 2017.[Abstract]


Salmonella infections and their gallstone associated biofilm infections are difficult to treat due to poor penetration of antibiotics into the intracellular compartments of macrophages and within biofilms. Here we developed ciprofloxacin loaded chitosan nanoparticles (cCNPs) and fucoidan (Fu) coated cCNPs (Fu-cCNPs). Characterizations of these nanoparticles were carried out using Dynamic Light Scattering‎, Transmission electron microscopy and Fourier transform infrared spectroscopy. The prepared cCNPs and Fu-cCNPs have the size range of 124±7nm and 320±18nm, respectively. Both nanoparticles were found to be non-hemolytic and cytocompatible. In vitro sustained release of ciprofloxacin was observed from both cCNPs and Fu-cCNPs over a period of 2 weeks. The antimicrobial activity of cCNPs and Fu-cCNPs was tested under in vitro and in vivo conditions. The intracellular anti-Salmonella activity of Fu-cCNPs was 2 fold higher than cCNPs and 6 fold higher than ciprofloxacin alone. Fluorescence microscopic images confirmed enhanced delivery of Fu-cCNPs than the cCNPs within the intracellular compartment of macrophages. Both cCNPs and Fu-cCNPs are found to be equally effective in dispersing Salmonella Paratyphi A gallstone biofilms. The in vivo antibacterial activities of Fu-cCNPs were superior to cCNPs which we have validated using Salmonella Paratyphi A infected Drosophila melanogaster fly model. Our overall results showed that (1) Fu-cCNPs are more effective in eradicating Salmonella infections than cCNPs; (2) both cCNPs and Fu-cCNPs were equally effective in dispersing Salmonella gallstone biofilms.

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2017

Journal Article

N. K. Gayathri, Aparna, V., Maya, S., Raja Biswas, Dr. Jayakumar Rangasamy, and C. Mohan, G., “Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles”, Carbohydrate Polymers, vol. 177, pp. 67 - 76, 2017.[Abstract]


We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were −7.3kcal/mol, −5.1kcal/mol and −8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery.

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2017

Journal Article

Dr. Jayakumar Rangasamy, S, M., Uthaman, S., Sarmento, B., and C, G. Mohan., “In vivo Evaluation of Cetuximab Conjugated γ-Poly (glutamic acid)-Docetaxel Nanomedicines in EGFR Overexpressing Gastric Cancer Xenograft”, International Journal of Nanomedicine, vol. 12, 2017.

2017

Journal Article

S. Xavier, S Ramaiyer, K., Panikar, D., Nair, S., Menon, K., and Dr. Lakshmi Sumitra, “62 Molecular Analysis of Epidermal Growth Factor Receptor Variant III and Glucose Transporter Expressions in Different Grades of Glioma: Potential biomarkers for Targeted Therapy”, Annals of Oncology, vol. 28, p. mdx511.028, 2017.[Abstract]


Background: Glioblastomas are highly resistant to the standard therapy owing to their metabolic aggressiveness [1]. These tumors are often marked by a radioresistant mutant, epidermal growth factor receptor variant III, EGFRvIII and its role in metabolic fueling has been implicated [2, 3]. In order to analyze their potential role in tumor progression, we aimed to evaluate the relationship between the expression levels of EGFRvIII and a brain glucose transporter (GLUT) and compared against the clinical grades of glioma.

Methods: Gliomas (n = 40) were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing methods for EGFRvIII detection. The EGFRvIII positive gliomas were analyzed for the gene expression levels of EGFRvIII and GLUT using real-time PCR assay and compared against the clinical grades using standard statistical tools. The protein level expressions of EGFR, EGFRvIII and GLUT were evaluated using immunohistochemistry in formalin fixed paraffin embedded (FFPE) sections of patient tumors.

Results: EGFRvIII was detected in 53% of the gliomas analyzed (Figure 1). Both EGFRvIII (p < 0.05) and GLUT (p < 0.05) showed significant upregulation in gene expressions among glioma patients. Interestingly, EGFRvIII showed strong positive correlation with GLUT (r = 0.865; p < 0.01). Most importantly, the levels of EGFRvIII (r = 0.838; p < 0.01) and GLUT (r = 0.771; p < 0.01) depicted significant positive correlation with the clinical grades of glioma. And the protein expressions of EGFR/EGFRvIII and GLUT were observed as regions of intense brown staining of FFPE sections of patient tumors by immunohistochemical evaluation.

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2017

Journal Article

S. Suresh, Unni, G. E., Ni, C., R. Sreedharan, S., R. Krishnan, R., Satyanarayana, M., Shanmugam, M., and Pillai, V. P. Mahadevan, “Phase modification and morphological evolution in Nb2O5 thin films and its influence in dye- sensitized solar cells”, Applied Surface Science, vol. 419, pp. 720 - 732, 2017.[Abstract]


Thermal energy plays a crucial role on the phase evolution of niobium oxide (Nb2O5) thin films and when employed as a blocking layer these films can manoeuvre charge transfer process in a dye sensitized solar cell (DSSC). Niobium oxide film, prepared by RF magnetron sputtering process, endured phase transitions successively from amorphous to orthorhombic and finally to monoclinic phases when subjected to post-deposition annealing. The co-existence of orthorhombic and monoclinic phases with an interesting surface morphology is perceived at an annealing temperature of 900°C. Nb2O5 blocking layer at the FTO/TiO2 interface strongly influenced the photovoltaic parameters of the DSSC and the blocking layer in the orthorhombic phase is found to be most effective in suppressing charge recombination and delivered a maximum efficiency of 7.33%. The improvement in open circuit voltage can be foreseeable as shifting of the Fermi level towards the conduction band edge of the TiO2 as a result of structural modification of the Nb2O5 blocking layer. The thermal stability of the FTO is also investigated and found that the electrical and optical properties of FTO were remarkably stable up to 600°C and begin to change appreciably from 700°C onwards.

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2017

Journal Article

S. Reddy Kasireddy, Gangaja, B., Shantikumar V. Nair, and Dr. Dhamodaran Santhanagopalan, “Mn4+ Rich Surface Enabled Elevated Temperature and Full-cell Cycling Performance of LiMn2O4 Cathode Material”, Electrochimica Acta, vol. 250, pp. 359 - 367, 2017.[Abstract]


LiMn2O4 (LMO) cathode exhibiting improved electrochemical performance is reported. X-ray diffraction confirms spinel cubic structure in the bulk with localized structural integrity confirmed by high-resolution Transmission Electron Microscopy (TEM) analysis showing lattice fringes with spacing of 0.48nm corresponding to (111) of spinel LMO. X-ray photoelectron spectroscopy (XPS) study quantified the Mn4+/Mn3+∼2 instead of 1 on the surface of pristine LMO nanoparticles. Mn4+ rich surface improved elevated temperature cycling stability inhibiting Mn-dissolution. The surface rich Mn4+ and almost equal concentration of Mn4+ and Mn3+ in the sub-surface/bulk was confirmed by XPS analysis upon ion-etching. At room temperature, high discharge capacity of ∼110 mAh/g at 2C rate and ∼102 mAh/g at 10C rate is reported for long cycles (over 500). Cycling at 55°C, capacity retention of 81.2% and 72% at the end of 200 cycles for 1C and 10C discharge rates respectively are testified for the electrochemical stability. This is superior elevated temperature performance of LMO electrodes especially, without any surface coating or doping. To demonstrate LMO cathode’s potential, a full-cell against Li4Ti5O12 and commercial graphite anodes were tested that exhibit discharge capacity of 95 mAh/g and 82 mAh/g respectively with retention of ∼82% over 100 cycles. Finally, electrodes after first charge and discharge have been investigated by ex situ XPS to correlate the oxidation states of manganese with pristine LMO.

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2017

Journal Article

B. Gangaja, Reddy, K. Siva, Nair, S., and Dr. Dhamodaran Santhanagopalan, “Impact of Carbon Nanostructures as Additives with Spinel Li4Ti5O12/LiMn2O4 Electrodes for Lithium Ion Battery Technology”, ChemistrySelect, vol. 2, pp. 9772-9776, 2017.[Abstract]


Abstract Spinel structured nanomaterials have shown good stability for lithium ion storage applications. Among all, Li4Ti5O12 (LTO) anode and LiMn2O4 (LMO) cathode is a potential combination for high energy and high power applications. In the present work, we utilize this specific combination to fabricate full-cells in combination with carbon nanostructures as additives. Typically, 20–25 nm sized LTO and 200–500 nm sized LMO nanoparticle electrodes are composited with carbon nanostructures including, carbon nanotube (CNT), carbon black (CB) and graphene nanoplatelets (GNP). High rate performance of respective half-cells (lithium metal as counter electrode) of LTO and LMO are tested up to 50C. It was found that half-cells with CNT additive retained almost 80% of its 1C rate capacity at 50C rate. Also both the electrodes exhibited 1000 cycles stability with retention of about 80% at 10C rate cycling. Using these CNT additive based electrodes, a full-cell fabricated and tested exhibited high capacity and stable cycling over 500 cycles at 1000 mA/g specific current. The full-cell delivered power density of about 2310 W/kg and energy density of about 140 Wh/kg that can be further improved for high power Li-ion battery technology.

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2017

Journal Article

D. T.D., S., M., Shantikumar V Nair, and A.K., R., “Surfactant-assisted Synthesis of Porous TiO2 Nanofibers as an Anode Material for Secondary Lithium ion Batteries”, Sustainable Energy and Fuels, vol. 1, pp. 138-144, 2017.[Abstract]


An optimized amount of cetyltrimethylammonium bromide (CTAB) as a surfactant was used for the first time to fabricate porous TiO2 nanofibers by an electrospinning technique combined with post-annealing at 500 °C for 5 h in air medium. The fabricated porous TiO2 nanofibers were systematically characterized by powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, surface area measurements and electrochemical testing. The porous TiO2 nanofibers contained numerous surface pores with an average diameter of ∼80–90 nm. As an anode, the porous TiO2 nanofiber electrode delivered not only a high reversible capacity and excellent cycle stability over 100 cycles but also excellent rate capability at various current rates in comparison to control TiO2 nanofibers (prepared in the absence of CTAB). The rapid transportation of lithium ions and reduced lithium ion diffusion length probably are responsible for the improved electrochemical performances of the porous TiO2 nanofiber electrode synthesized in the presence of the CTAB surfactant.

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2017

Journal Article

S. B.N., S.R., S., A.G, M., and Shantikumar V Nair, “Designing Scaffolds for Bone Tissue Engineering”, Translating Biomaterials for Bone Graft: Bench-Top to Clinical Applications, 2017.[Abstract]


Tissue engineering has been described as “an interdisciplinary field that applies the principles of engineering and life science towards the development of biological substitutes that restore, maintain, or improve tissue or organ function.”1 The history of this emerging field began in the early 1970s and gained popularity in the 1980s through the experimental initiatives of Langer and Vacanti.2 In 1993, Langer and Vacanti described the utilization of a branching network of synthetic biocompatible/biodegradable polymers configured as scaffolds seeded with viable cells, a seminal paper that became the foundation for current advances in the field of tissue engineering.1

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2017

Journal Article

V. Jeseentharani, Pugazhenthiran, N., Mathew, A., Chakraborty, I., Baksi, A., Ghosh, J., Jash, M., Anjusree, G. S., Deepak, T. G., A. Nair, S., and Pradeep, T., “Atomically Precise Noble Metal Clusters Harvest Visible Light to Produce Energy”, ChemistrySelect, vol. 2, pp. 1454-1463, 2017.[Abstract]


Abstract Atomically precise gold and silver clusters are a new class of sensitizers which can be used as substitutes for dyes in the classical dye-sensitized solar cells (DSCs). Here noble metal clusters protected by proteins and thiols (Au30@BSA, Au25SBB18, and Ag44MBA30) have been used for photovoltaic studies. These metal clusters were used as sensitizers for the photoanodes fabricated using TiO2 nanotubes (NTs) and the commercial P25 TiO2 nanoparticles. The TiO2, clusters and the solar cells were characterized by spectroscopy, microscopy, current-voltage (I-V) and incident photon-to-current conversion efficiency (IPCE) measurements. A systematic I-V study revealed a conversion efficiency of 0.35 % for the Au30@BSA sensitized solar cell made from TiO2 NTs which showed an IPCE maximum of 3 % at ∼ 400 nm.

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2016

Journal Article

M. N. Sundaram, Sowmya, S., Deepthi, S., Bumgardener, J. D., and Dr. Jayakumar Rangasamy, “Bilayered Construct for Simultaneous Regeneration of Alveolar Bone and Periodontal Ligament”, Journal of Biomedical Materials Research - Part B Applied Biomaterials, 2016.[Abstract]


Periodontitis is an inflammatory disease that causes destruction of tooth-supporting tissues and if left untreated leads to tooth loss. Current treatments have shown limited potential for simultaneous regeneration of the tooth-supporting tissues. To recreate the complex architecture of the periodontium, we developed a bilayered construct consisting of poly(caprolactone) (PCL) multiscale electrospun membrane (to mimic and regenerate periodontal ligament, PDL) and a chitosan/2wt % CaSO<inf>4</inf> scaffold (to mimic and regenerate alveolar bone). Scanning electron microscopy results showed the porous nature of the scaffold and formation of beadless electrospun multiscale fibers. The fiber diameter of microfiber and nanofibers was in the range of 10±3 μm and 377±3 nm, respectively. The bilayered construct showed better protein adsorption compared to the control. Osteoblastic differentiation of human dental follicle stem cells (hDFCs) on chitosan/2wt % CaSO<inf>4</inf> scaffold showed maximum alkaline phosphatase at seventh day followed by a decline thereafter when compared to chitosan control scaffold. Fibroblastic differentiation of hDFCs was confirmed by the expression of PLAP-1 and COL-1 proteins which were more prominent on PCL multiscale membrane in comparison to control membranes. Overall these results show that the developed bilayered construct might serve as a good candidate for the simultaneous regeneration of the alveolar bone and PDL. © 2015 Wiley Periodicals, Inc.

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2016

Journal Article

M. Chatterjee, Anju, C. P., Biswas, L., V. Kumar, A., Dr. Gopi Mohan C., and Raja Biswas, “Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options”, International Journal of Medical Microbiology, vol. 306, pp. 48 - 58, 2016.[Abstract]


Pseudomonas aeruginosa is a leading cause of nosocomial infections and is responsible for ∼10% of all hospital-acquired infections worldwide. It continues to pose a therapeutic challenge because of the high rate of morbidity and mortality associated with it and the possibility of development of drug resistance during therapy. Standard antibiotic regimes against P. aeruginosa are increasingly becoming ineffective due to the rise in drug resistance. With the scope for developing new antibiotics being limited, alternative treatment options are gaining more and more attention. A number of recent studies reported complementary and alternative treatment options to combat P. aeruginosa infections. Quorum sensing inhibitors, phages, probiotics, anti-microbial peptides, vaccine antigens and antimicrobial nanoparticles have the potential to act against drug resistant strains. Unfortunately, most studies considering alternative treatment options are still confined in the pre-clinical stages, although some of these findings have tremendous potential to be turned into valuable therapeutics. This review is intended to raise awareness of several novel approaches that can be considered further for combating drug resistant P. aeruginosa infections. © 2015 Elsevier GmbH.

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2016

Journal Article

P. Geetha, Sivaram, A. J., Dr. Jayakumar Rangasamy, and Dr. Gopi Mohan C., “Integration of in silico modeling, prediction by binding energy and experimental approach to study the amorphous chitin nanocarriers for cancer drug delivery”, Carbohydrate Polymers, vol. 142, pp. 240-249, 2016.[Abstract]


In silico modeling of the polymer-drug nanocarriers have now days became a powerful virtual screening tool for the optimization of new drug delivery systems. The interactions between amorphous chitin nanoparticles (AC-NPs) with three different types of anti-cancer drugs such as curcumin, docetaxel and 5-flurouracil were studied by integration of computational and experimental techniques. The drug entrapment and drug loading efficiency of these three drugs with AC-NPs were (98 ± 1%), (77 ± 2%), and (47 ± 12%), respectively. Further, cytotoxicity and cellular uptake studies of drug loaded AC-NPs on Gastric adenocarcinoma (AGS) cells showed enhanced drug uptake and cancer cell death. In silico binding energy (BE) between AC-NPs with these anti-cancer drugs were studied by molecular docking technique. Computational drug's BEs are in excellent agreement with experimental AC-NPs drug loading (R2 = 0.9323) and drug entrapment (R2 = 0.9741) efficiencies. Thus, present integrated study revealed significant insight on chemical nature, strength, and putative interacting sites of anti-cancer drugs with AC-NPs. © 2016 Elsevier Ltd. All rights reserved.

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2016

Journal Article

A. J, Kuttappan, S., Keyan, K. S., and Dr. Manitha B. Nair, “Evaluation of osteoinductive and endothelial differentiation potential of Platelet-Rich Plasma incorporated Gelatin-Nanohydroxyapatite Fibrous Matrix”, Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 104, no. 4, pp. 771-781, 2016.[Abstract]


In this study, platelet-rich plasma (PRP) was incorporated into gelatin-nanohydroxyapatite fibrous scaffold in two forms (PRP gel as coating on the scaffold [PCSC] and PRP powder within the scaffold [PCSL] and investigated for (a) growth factor release; (b) stability of scaffold at different temperature; (c) stability of scaffold before and after ETO sterilization; and (d) osteogenic and endothelial differentiation potential using mesenchymal stem cells (MSCs). PCSC demonstrated a high and burst growth factor release initially followed by a gradual reduction in its concentration, while PCSL showed a steady state release pattern for 30 days. The stability of growth factors released from PCSL was not altered either through ETO sterilization or through its storage at different temperature. PRP-loaded scaffolds induced the differentiation of MSCs into osteogenic and endothelial lineage without providing any induction factors in the cell culture medium and the differentiation rate was significantly higher when compared to the scaffolds devoid of PRP. PCSC performed better than PCSL. In general, PRP in combination with composite fibrous scaffold could be a promising candidate for bone tissue engineering applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 771–781, 2016.

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2016

Journal Article

V. Dhanalakshmi, Nimal, T. R., Dr. Sabitha M., Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Skin and muscle permeating antibacterial nanoparticles for treating Staphylococcus aureus infected wounds”, Journal of Biomedical Materials Research - Part B Applied Biomaterials, 2016.[Abstract]


Majority of the chronic wounds are infected with bacteria like Staphylococcus aureus (S. aureus). The deep tissue infections are difficult to treat using topical antibiotics, due to their poor tissue penetration. In order to treat S. aureus deep tissue infections we have developed an antibiotic delivery system using chitosan nanoparticles (CNPs). To enhance their tissue penetration these CNPs were further coated using lecithin (CLNPs). Antibiotic tigecycline was loaded into chitosan nanoparticles (tCNPs) and then coated with lecithin to generate lecithin coated tigecycline loaded chitosan nanoparticles (tCLNPs). The prepared nanoparticles were characterized using DLS, SEM, TEM and FT-IR. The prepared CNPs, tCNPs, CLNPs and tCLNPs have the size range of 85±10, 90±18, 188±5 and 235±20 nm, respectively. The tCLNPs shows more sustained release pattern of tigecycline. The antibacterial activity of the developed nanoparticles was confirmed against laboratory and clinical strains of S. aureus using in vitro and ex vivo experiments. The ex vivo skin and muscle permeation study ensures the enhanced delivery of tigecycline to the deeper tissue. The prepared nanoparticles were hemo-compatible and cyto-compatible. Our study suggests that the prepared tCLNPs can be effectively used for the treatment of S. aureus infected wounds. © 2016 Wiley Periodicals, Inc.

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2016

Journal Article

D. Joseph and Kumar, S., “Identifying clues to molecular etiology of multiple sclerosis in South Indian patients”, Multiple Sclerosis and Related Disorders, vol. 5, pp. 7-11, 2016.[Abstract]


Background: Environmental risk factors have a dominant role in the pathogenesis of multiple sclerosis (MS). Unhealthy lifestyle can predispose people to autoimmune diseases. MS was a rare disease in Kerala, but now, we notice frequent cases of MS at the city neurology clinic. Changing lifestyle and associated changes in the level of proinflammatory biomolecules like: leptin, soluble leptin receptor (SLR) and free fatty acids (FA) could be contributing to rise in MS incidence. Objective: To identify variations in the levels of bio-molecules: leptin, SLR and FA, between MS patients and matched healthy control. Method: Leptin and SLR levels in the blood serum, were estimated using ELISA, while total FA levels, were estimated using an enzyme based calorimetric assay. Result: Mean serum FA levels in MS patients (31.39±4.83 nmole/100 μl) were 2.7 fold higher than controls (11.54±2.66 nmoles/100 μl) at more than 99% CI. The differences in mean leptin and SLR levels were not statistically significant. Conclusion: MS patients had high level of total FA in their blood. High FA in blood may have a role in MS pathogenesis. More in-depth study is required to understand the precise mechanism by which FA rise in MS blood sample can contribute to pathogenesis. © 2015 Elsevier B.V. All rights reserved.

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2016

Journal Article

N. S. Rejinold, Thomas, R. G., Muthiah, M., Lee, H. J., Jeong, Y. Y., Park, I. - K., and Dr. Jayakumar Rangasamy, “Breast Tumor Targetable Fe3O4 Embedded Thermo-responsive Nanoparticles for Radiofrequency Assisted Drug Delivery”, Journal of Biomedical Nanotechnology, vol. 12, pp. 43-55, 2016.[Abstract]


Non-invasive radiofrequency (RF) frequency may be utilized as an energy source to activate thermo-responsive nanoparticles for the controlled local delivery of drugs to cancer cells. Herein, we demonstrate that 180 ±20 nm sized curcumin encapsulated chitosan-grraft-poly(/V-vinyl caprolactam) nanoparticles containing iron oxide nanoparticles (Fe3O4-CRC-TRC-NPs) were selectively internalized in cancer cells in vivo. Using an RF treatment at 80 watts for 2 min, Fe3O4-CRC-TRC-NPs, dissipated heat energy of 42 °C, which is the lower critical solution temperature (LCST) of the chitosan-grraft-poly(/V-vinyl caprolactam), causing controlled curcumin release and apoptosis to cultured 4T1 breast cancer cells. Further, the tumor localization studies on orthotopic breast cancer model revealed that Fe3O4-CRC-TRC-NPs selectively accumulated at the primary tumor as confirmed by in vivo live imaging followed by ex vivo tissue imaging and HPLC studies. These initial results strongly support the development of RF assisted drug delivery from nanoparticles for improved tumor targeting for breast cancer treatment. Copyright © 2016 American Scientific Publishers All rights reserved.

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2016

Journal Article

Aab Sasidharan, Swaroop, Sa, Chandran, Pab, Shantikumar V Nair, and Dr. Manzoor K., “Cellular and molecular mechanistic insight into the DNA-damaging potential of few-layer graphene in human primary endothelial cells”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 12, pp. 1347-1355, 2016.[Abstract]


Despite graphene being proposed for a multitude of biomedical applications, there is a dearth in the fundamental cellular and molecular level understanding of how few-layer graphene (FLG) interacts with human primary cells. Herein, using human primary umbilical vein endothelial cells as model of vascular transport, we investigated the basic mechanism underlying the biological behavior of graphene. Mechanistic toxicity studies using a battery of cell based assays revealed an organized oxidative stress paradigm involving cytosolic reactive oxygen stress, mitochondrial superoxide generation, lipid peroxidation, glutathione oxidation, mitochondrial membrane depolarization, enhanced calcium efflux, all leading to cell death by apoptosis/necrosis. We further investigated the effect of graphene interactions using cDNA microarray analysis and identified potential adverse effects by down regulating key genes involved in DNA damage response and repair mechanisms. Single cell gel electrophoresis assay/Comet assay confirmed the DNA damaging potential of graphene towards human primary cells. © 2016 Elsevier Inc.

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2016

Journal Article

S. Padmakumar, Joseph, J., Neppalli, M. H., Mathew, S. E., Shantikumar V Nair, Dr. Sahadev Shankarappa, and Menon, D., “Electrospun Polymeric Core-sheath Yarns as Drug Eluting Surgical Sutures”, ACS Applied Materials and Interfaces, vol. 8, pp. 6925-6934, 2016.[Abstract]


Drug-coated sutures are widely used as delivery depots for antibiotics and anti-inflammatory drugs at surgical wound sites. Although drug-laden coating provides good localized drug concentration, variable loading efficiency and release kinetics limits its use. Alternatively, drug incorporation within suture matrices is hampered by the harsh fabrication conditions required for suture-strength enhancement. To circumvent these limitations, we fabricated mechanically robust electrospun core-sheath yarns as sutures, with a central poly-l-lactic acid core, and a drug-eluting poly-lactic-co-glycolic acid sheath. The electrospun sheath was incorporated with aceclofenac or insulin to demonstrate versatility of the suture in loading both chemical and biological class of drugs. Aceclofenac and insulin incorporated sutures exhibited 15% and 4% loading, and release for 10 and 7 days, respectively. Aceclofenac sutures demonstrated reduced epidermal hyperplasia and cellularity in skin-inflammation animal model, while insulin loaded sutures showed enhanced cellular migration in wound healing assay. In conclusion, we demonstrate an innovative strategy of producing mechanically strong, prolonged drug-release sutures loaded with different classes of drugs. © 2016 American Chemical Society. More »»

2016

Journal Article

S. Deepthi, Venkatesan, J., Kim, S. - K., Bumgardner, J. D., and Dr. Jayakumar Rangasamy, “An overview of chitin or chitosan/nano ceramic composite scaffolds for bone tissue engineering”, International Journal of Biological Macromolecules, 2016.[Abstract]


Chitin and chitosan based nanocomposite scaffolds have been widely used for bone tissue engineering. These chitin and chitosan based scaffolds were reinforced with nanocomponents viz Hydroxyapatite (HAp), Bioglass ceramic (BGC), Silicon dioxide (SiO2), Titanium dioxide (TiO2) and Zirconium oxide (ZrO2) to develop nanocomposite scaffolds. Plenty of works have been reported on the applications and characteristics of the nanoceramic composites however, compiling the work done in this field and presenting it in a single article is a thrust area. This review is written with an aim to fill this gap and focus on the preparations and applications of chitin or chitosan/nHAp, chitin or chitosan/nBGC, chitin or chitosan/nSiO2, chitin or chitosan/nTiO2 and chitin or chitosan/nZrO2 in the field of bone tissue engineering in detail. Many reports so far exemplify the importance of ceramics in bone regeneration. The effect of nanoceramics over native ceramics in developing composites, its role in osteogenesis etc. are the gist of this review. © 2016 Elsevier B.V. More »»

2016

Journal Article

A. R. Kumar, Sivashanmugam, A., Deepthi, S., Bumgardner, J. D., Nair, S. V., and Dr. Jayakumar Rangasamy, “Nano-fibrin stabilized CaSO4 crystals incorporated injectable chitin composite hydrogel for enhanced angiogenesis & osteogenesis”, Carbohydrate Polymers, vol. 140, pp. 144-153, 2016.[Abstract]


Calcium sulfate (CaSO4), an excellent biodegradable bone forming agent that is an ideal choice as additive in gels, however, its disadvantage being poor gel rheology and angiogenesis. Here, we have synthesized chitin-CaSO4-nano-fibrin based injectable gel system which shows improved rheology and angiogenic potential. Rheological studies showed that the composite gel was a shear thinning gel with elastic modulus of 15.4 ± 0.275 kPa; a 1.67 fold increase over chitin control. SEM and XRD analyses revealed the effect of nano-fibrin (nFibrin) in transforming CaSO4 crystal shape from needle to hexagonal. It also masked the retarding effect of CaSO4 towards in vitro early cell attachment and angiogenesis using rabbit adipose derived mesenchymal stem cells (rASCs) and HUVECs, respectively. rASCs osteogenesis was confirmed by spectrophotometric endpoint assay, which showed 6-fold early increase in alkaline phosphatase levels and immuno-cytochemistry analysis. These in vitro results highlight the potential of injectable chitin-CaSO4-nFibrin gel for osteo-regeneration via enhanced angiogenesis.

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2016

Journal Article

S. Ravi and Vadukumpully, S., “Sustainable carbon nanomaterials: Recent advances and its applications in energy and environmental remediation”, Journal of Environmental Chemical Engineering, vol. 4, pp. 835-856, 2016.[Abstract]


Carbon nanomaterials represent one of the most diverse classes of materials with exceptional range of properties, which make them suitable for applications in widespread areas of research. There is an incisive need to look for new carbon nanostructures via sustainable and low-cost methods realizing their role in energy and environmental applications. Most of the conventional preparation strategies involve energy intensive conditions and hence high cost of production. In this regard, green synthesis of carbon nanomaterials via cost-effective strategies derives great relevance. Natural resources, particularly biomass; waste residues like industrial effluents and plastics can generate carbon nanomaterials. This review presents some of the recent advances in the synthesis of various carbon nanomaterials from sustainable resources and outlines their applications in energy storage, environmental remediation and purification. © 2016 Published by Elsevier Ltd.

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2016

Journal Article

S. Mohapatra, Shantikumar V Nair, Dr. Dhamodaran Santhanagopalan, and Alok Kumar Rai, “Nanoplate and mulberry-like porous shape of CuO as anode materials for secondary lithium ion battery”, Electrochimica Acta, vol. 206, pp. 217-225, 2016.[Abstract]


Facile hydrothermal synthesis of nanoplate and mulberry-like porous shape of CuO nanostructures was developed as anode materials for application in lithium ion batteries. The powder X-ray diffraction patterns of both the samples were indexed well to a pure monoclinic phase of CuO with no impurities. The CuO sample synthesized at different pH and reaction temperature exhibited nanoplate with average width and length of ∼150-300 nm and ∼300-700 nm and mulberry-like porous shape of CuO with average length of ∼300-400 nm. Electrochemical tests show that the lithium storage performances of both the nanoplate and mulberry-like samples are influenced more closely to its structural aspects than their morphology and size factors. The CuO nanoplate electrode exhibits high reversible charge capacity of 279.3 mAh g-1 at 1.0C after 70 cycles, and a capacity of 150.2 mAh g-1 even at high current rate of 4.0C during rate test, whereas the mulberry-like porous shape of CuO anode delivers only 131.4 mAh g-1 at 1.0C after 70 cycles and 121.7 mAh g-1 at 4.0C. It is believed that the nanoplate type architecture is very favorable to accommodate the volume expansion/contraction and aggregation of particles during the cyclic process. In contrast, the mulberry-like porous morphology could not preserve the integrity of the structure and completely disintegrated into nanoparticles during Li+ ion insertion/deinsertion due to the loose contact between the particles. © 2016 Elsevier Ltd. All rights reserved.

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2016

Journal Article

Rajitha Panonnummal, Gopinath, D., Dr. Raja Biswas, Dr. Sabitha M., and Dr. Jayakumar Rangasamy, “Chitosan nanoparticles in drug therapy of infectious and inflammatory diseases”, Expert Opinion on Drug Delivery, vol. 13, no. 8, pp. 1177-1194, 2016.[Abstract]


Introduction: Chitosan, a polymer from the chitin family has diverse pharmaceutical and bio-medical utility because of its easy widespread availability, non-toxicity, biocompatibility, biodegradability, rich functionalities and high drug-loading capacity. Recent pharmaceutical research has examined the use of chitosan-based systems for drug delivery applications in various diseases. The availability of functional groups permits the conjugation of specific ligands and thus helps to target loaded drugs to the site of infection/inflammation. Slow biodegradation of chitosan permits controlled and sustained release of loaded moieties; reduces the dosing frequency and is useful for improving patient compliance in infectious drug therapy. The muco-adhesion offered by chitosan makes it an attractive candidate for anti-inflammatory drug delivery, where rapid clearance of the active moiety due to the increased tissue permeability is the major problem. The pH-dependent swelling and drug release properties of chitosan present a means of passive targeting of active drug moieties to inflammatory sites. Areas covered: Development of chitosan-based nanoparticulate systems for drug delivery applications is reviewed. The current state of chitosan-based nanosystems; with particular emphasis on drug therapy in inflammatory and infectious diseases is also covered. Expert opinion: The authors believe that chitosan-based nanosystems, due to the special and specific advantages, will have a promising role in the management of infectious and inflammatory diseases. © 2016 Informa UK Limited, trading as Taylor &amp; Francis Group

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2016

Journal Article

P. Preetham, Mohapatra, S., Shantikumar V Nair, Dr. Dhamodaran Santhanagopalan, and Alok Kumar Rai, “Ultrafast pyro-synthesis of NiFe2O4 nanoparticles within a full carbon network as a high-rate and cycle-stable anode material for lithium ion batteries”, RSC Advances, vol. 6, pp. 38064-38070, 2016.[Abstract]


NiFe2O4 nanoparticles fully anchored within a carbon network were prepared via a facile pyro-synthesis method without using any conventional carbon sources. The surface morphology was investigated using field-emission scanning electron microscopy, which confirmed the full anchoring of NiFe2O4 nanoparticles within a carbon network. The primary particle size of NiFe2O4 is in the range of 50-100 nm. The influence of the carbon network on the electrochemical performance of the NiFe2O4/C nanocomposite was investigated. The electrochemical results showed that the NiFe2O4/C anode delivered a reversible capacity of 381.8 mA h g-1 after 100 cycles at a constant current rate of 1.0C, and when the current rate is increased to a high current rate of 5.0C, a reversible capacity of 263.7 mA h g-1 is retained. The obtained charge capacity at high current rates is better than the reported values for NiFe2O4 nanoparticles. The enhanced electrochemical performance can be mainly ascribed to the high electrical conductivity of the electrode, the short diffusion path for Li+ ion transportation in the active material and synergistic effects between the NiFe2O4 nanoparticles and carbon network, which buffers the volume changes and prevents aggregation of NiFe2O4 nanoparticles during cycling. © The Royal Society of Chemistry 2016.

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2016

Journal Article

K. M. Sajesh, Kiran, K., Shantikumar V Nair, and Dr. Jayakumar Rangasamy, “Sequential layer-by-layer electrospinning of nano SrCO3/PRP loaded PHBV fibrous scaffold for bone tissue engineering”, Composites Part B: Engineering, vol. 99, pp. 445-452, 2016.[Abstract]


Development of scaffolds with a blend of osteoinductive and osteoconductive properties is believed to be an effective approach towards bone regeneration. In our current research, a biodegradable Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) [PHBV]/nano strontium carbonate/Platelet Rich Plasma (PRP) composite scaffold was fabricated using sequential layer-by-layer electrospinning method. The synthesized nSrCO3 nanoparticles were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and further the developed electrospun scaffolds were taken for in vitro assessments. Fiber diameter of the composite fibrous scaffold ranges from 400 to 800 nm. Cell proliferation analysis signifies the role of PRP in the developed scaffold. Osteogenic differentiation of hMSCs was confirmed by measuring the ALP concentration and mineral deposition on the scaffolds and demonstrates considerable enhancement on the composite scaffold. These preliminary results demonstrate that the developed electrospun biocomposite scaffold could serve as a better platform for bone regeneration. More »»

2016

Journal Article

Za Wang, Dr. Dhamodaran Santhanagopalan, Zhang, Wc, Wang, Fc, Xin, H. Lc, He, Kc, Li, Jd, Dudney, Nd, and Meng, Y. Sa, “In situ STEM-EELS observation of nanoscale interfacial phenomena in all-solid-state batteries”, Nano Letters, vol. 16, pp. 3760-3767, 2016.[Abstract]


Behaviors of functional interfaces are crucial factors in the performance and safety of energy storage and conversion devices. Indeed, solid electrode-solid electrolyte interfacial impedance is now considered the main limiting factor in all-solid-state batteries rather than low ionic conductivity of the solid electrolyte. Here, we present a new approach to conducting in situ scanning transmission electron microscopy (STEM) coupled with electron energy loss spectroscopy (EELS) in order to uncover the unique interfacial phenomena related to lithium ion transport and its corresponding charge transfer. Our approach allowed quantitative spectroscopic characterization of a galvanostatically biased electrochemical system under in situ conditions. Using a LiCoO2/LiPON/Si thin film battery, an unexpected structurally disordered interfacial layer between LiCoO2 cathode and LiPON electrolyte was discovered to be inherent to this interface without cycling. During in situ charging, spectroscopic characterization revealed that this interfacial layer evolved to form highly oxidized Co ions species along with lithium oxide and lithium peroxide species. These findings suggest that the mechanism of interfacial impedance at the LiCoO2/LiPON interface is caused by chemical changes rather than space charge effects. Insights gained from this technique will shed light on important challenges of interfaces in all-solid-state energy storage and conversion systems and facilitate improved engineering of devices operated far from equilibrium. More »»

2016

Journal Article

S. Va Nair, Baranwal, Ga, Chatterjee, Ma, Sachu, Ac, Dr. Anil Kumar V., Chinchu Bose, Dr. Asoke Banerji, and Dr. Raja Biswas, “Antimicrobial activity of plumbagin, a naturally occurring naphthoquinone from Plumbago rosea, against Staphylococcus aureus and Candida albicans”, International Journal of Medical Microbiology, vol. 306, pp. 237-248, 2016.[Abstract]


Candida albicans and Staphylococcus aureus are opportunistic pathogens. Despite causing a number of independent infections, both pathogens can co-infect to cause urinary tract infections, skin infections, biofilm associated infections, sepsis and pneumonia. Infections of these two pathogens especially their biofilm associated infections are often difficult to treat using currently available anti-bacterial and anti-fungal agents. In order to identify a common anti-microbial agent which could confer a broad range of protection against their infections, we screened several phytochemicals and identified plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a phytochemical from Plumbago species as a potent antimicrobial agent against S. aureus and C. albicans, with a minimum inhibitory concentration of 5 μg/ml. Antimicrobial activity of plumbagin was validated using an ex-vivo porcine skin model. For better understanding of the antimicrobial activity of plumbagin, a Drosophila melanogaster infection model was used, where D. melanogaster was infected using S. aureus and C. albicans, or with both organisms. The fly's survival rate was dramatically increased when infected flies were treated using plumbagin. Further, plumbagin was effective in preventing and dispersing catheter associated biofilms formed by these pathogens. The overall results of this work provides evidence that plumbagin, possesses an excellent antimicrobial activity which should be explored further for the treatment of S. aureus and C. albicans infections. © 2016 Elsevier GmbH.

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2016

Journal Article

S. Deepthi and Dr. Jayakumar Rangasamy, “Prolonged release of TGF-β from polyelectrolyte nanoparticle loaded macroporous chitin-poly(caprolactone) scaffold for chondrogenesis”, International Journal of Biological Macromolecules, 2016.[Abstract]


Cartilage degeneration occurs when the catabolic factors overtakes the anabolic factors. The regeneration capability of damaged cartilage is poor due to its hypovascular and hypocellular tissue. Tissue engineering strategies aims in development of a suitable substrate that provide the required physical, chemical and biological cues to the proliferating cells to direct chondrogenesis. A macroporous polymeric blend scaffold of chitin and poly(caprolactone) (PCL) was fabricated by lyophilisation technique and characterized using Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric/Differential thermal Analysis (TG/DTA). The effect of prolonged release of Transforming growth factor-β (TGF-β) was studied by encapsulating it in chondroitin sulphate nanoparticles (nCS) incorporated in chitin-PCL scaffold. Chondroitin sulphate nanoparticles containing TGF-β (TGF-β-nCS) was developed by polyelectrolyte crosslinking using chitosan. Characterization of TGF-β-nCS by Dynamic Light Scattering particle sizer and SEM showed a 230. ±. 20. nm sized spherical particles. Swelling and degradation studies of the composite scaffold showed its stability. Protein adsorption was enhanced in nanoparticle containing scaffold. The effect of TGF-β was well addressed by the increased attachment and proliferation of rabbit adipose derived mesenchymal stem cells (rASCs). The chondrogenic potential of rASCs in the presence of TGF-β releasing composite scaffold showed an increased proteoglycan deposition. These studies highlight the positive effects of chitin-PCL-TGF-β-nCS scaffold for cartilage regeneration. © 2016 Elsevier B.V.

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2016

Journal Article

Da Damien, Anjusree, G. Sb, Nair, AbSreekumara, and Shaijumon, M. Ma, “TiO2 fibre/particle nanohybrids as efficient anodes for lithium-ion batteries”, RSC Advances, vol. 6, pp. 45802-45808, 2016.[Abstract]


We report the synthesis of a TiO2 nanohybrid with a unique morphology consisting of TiO2 nanoparticles decorating the surface of TiO2 nanofibers, obtained by a simultaneous electrospinning and electrospraying technique, and its electrochemical studies as efficient anodes for the Li-ion battery. The TiO2-fiber/particle composite electrode exhibited a very high discharge capacity (190 mA h g-1 after 50 cycles, at C/10), excellent rate capability with remarkable capacity retention of 77% of initial capacity at 5C rate, and good cyclic stability, compared to TiO2 nanofibers and nanoparticles. The capacitive contribution from these electrodes is studied in detail by using cyclic voltammetry measurements, and the results are correlated with the overall electrochemical performance of the electrodes. The exceptional electrochemical characteristics exhibited by the TiO2-fiber/particle composite electrode, synthesized through a low-cost and scalable electrospinning technique, make it an ideal anode material for large-scale Li-ion battery applications. © The Royal Society of Chemistry 2016.

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2016

Journal Article

S. Deepthi, Gafoor, A. A. Abdul, Sivashanmugam, A., Shantikumar V Nair, and Dr. Jayakumar Rangasamy, “Nanostrontium ranelate incorporated injectable hydrogel enhanced matrix production supporting chondrogenesis: In vitro”, Journal of Materials Chemistry B, vol. 4, pp. 4092-4103, 2016.[Abstract]


An injectable hydrogel, with the advantage of adaptability to defect sites, patient compliance, controlled flowability and high water uptake capability, was explored as a prototype for cartilage tissue regeneration. Chitosan and fibrin are natural biomaterials that are biocompatible, biodegradable, resemble the ECM of the tissues and contain cell adhesion sites thereby providing a support for cell growth. In this study strontium ranelate, a drug recently studied to enhance cartilage regeneration, was encapsulated in chitosan nanoparticles to provide sustained delivery of the drug content within the composite gel (chitosan/alginate/fibrin hydrogel). The developed nanocomposite gel was characterized using SEM, EDS and FTIR. The particle size of the strontium ranelate loaded chitosan nanoparticles was found to be 160 ± 30 nm. The encapsulation and loading efficiency values of strontium ranelate were found to be 40 ± 10% and 36 ± 2% respectively. Rheological data showed a storage modulus of 5.514 ± 0.102 kPa with thermal stability over the studied temperature range, and the gel properties could be restored within 10 s after the application of a high shear rate. The cytocompatibility and chondrogenic potential was analyzed using human mesenchymal stem cells (hMSCs) to evaluate the applicability of the developed hydrogel for cartilage regeneration. hMSCs were found to be viable in the developed hydrogels and chondrogenic differentiation of hMSCs was observed which was confirmed with enhanced proteoglycan and collagen synthesis. These results indicated that the developed injectable nanocomposite gel would be a suitable system for cartilage regeneration. © 2016 The Royal Society of Chemistry.

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2016

Journal Article

V. M Priya, Sabitha, M., and Jayakumar, R., “Colloidal chitin nanogels: A plethora of applications under one shell.”, Carbohydr Polym, vol. 136, pp. 609-17, 2016.[Abstract]


<p>Chitin nanogels (CNGs) are a relatively new class of natural polymeric nanomaterials which have a large potential in the field of drug delivery and nanotherapeutics. These nanogels being very biocompatible are non-toxic when internalized by cells. In this review various properties, preparation techniques and applications of CNGs have been described. CNGs because of their nano-size possess certain unique properties which enable them to be used in a number of biomedical applications. CNGs are prepared by simple regeneration technique without using any cross-linkers. Various polymers, drugs and fluorescent dyes can be blended or incorporated or labelled with the chitin hydrogel network. Drugs and molecules encapsulated within CNGs can be used for targeted delivery, in vivo monitoring or even for therapeutic purposes. Here various applications of CNGs in the field of drug delivery, imaging, sensing and therapeutics have been discussed. </p>

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2016

Journal Article

G. Divya, Panonnummal, R., Gupta, S., Jayakumar, R., and Sabitha, M., “Acitretin and aloe-emodin loaded chitin nanogel for the treatment of psoriasis.”, Eur J Pharm Biopharm, vol. 107, pp. 97-109, 2016.[Abstract]


<p>The present study focuses on the development of an effective topical nanogel formulation of two anti-psoriatic drugs; Acitretin (Act) and Aloe-emodin (AE) using natural polymer chitin. Simple regeneration chemistry was used to prepare Chitin Nanogel Systems (CNGs). The developed control chitin (CNGs) nanogels, acitretin loaded chitin nanogels (ActCNGs) and aloe-emodin loaded chitin nanogels (AECNGs) were characterized by DLS, SEM, FTIR, XRD and TG-DTA. The systems were found to be spherical in shape with a size range of 98±10, 138±8 and 238±6nm having zeta potential values of +28±3, +27±3 and +25±6mV for CNGs, ActCNGs and AECNGs respectively. The in vitro haemolysis assay revealed that all the nanogel systems are blood compatible. The systems exhibited higher swelling and release at acidic pH. The ex vivo skin permeation studies using porcine skin confirmed the higher deposition of the systems at epidermal and dermal layers, which was confirmed further by fluorescent imaging. The in vivo anti-psoriatic activity study using Perry's mouse tail model and skin safety studies confirmed the potential benefit of the system for topical delivery of acitretin and aloe-emodin in psoriasis. </p>

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2016

Journal Article

S. Kuttappan, Mathew, D., and Nair, M. B., “Biomimetic composite scaffolds containing bioceramics and collagen/gelatin for bone tissue engineering - A mini review.”, Int J Biol Macromol, vol. 93, no. Pt B, pp. 1390-1401, 2016.[Abstract]


<p>Bone is a natural composite material consisting of an organic phase (collagen) and a mineral phase (calcium phosphate, especially hydroxyapatite). The strength of bone is attributed to the apatite, while the collagen fibrils are responsible for the toughness and visco-elasticity. The challenge in bone tissue engineering is to develop such biomimetic composite scaffolds, having a balance between biological and biomechanical properties. This review summarizes the current state of the field by outlining composite scaffolds made of gelatin/collagen in combination with bioactive ceramics for bone tissue engineering application.</p>

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2016

Journal Article

V. M Priya, Sivshanmugam, A., Boccaccini, A. R., Goudouri, O. M., Sun, W., Hwang, N., Deepthi, S., Nair, S. V., and Jayakumar, R., “Injectable osteogenic and angiogenic nanocomposite hydrogels for irregular bone defects.”, Biomed Mater, vol. 11, no. 3, p. 035017, 2016.[Abstract]


<p>Injectable hydrogels with their 3D structure and good moldability serve as excellent scaffolding material for regenerating irregular non load-bearing bone defects. Most of the bone defects do not heal completely due to the lack of vasculature required for the transport of nutrients and oxygen to the regenerating tissues. To enhance vasculature, we developed an injectable hydrogel system made of chitin and poly (butylene succinate) (PBSu) loaded with 250  ±  20 nm sized fibrin nanoparticles (FNPs) and magnesium-doped bioglass (MBG). FNPs were expected to enhance vascularisation and MBG was expected to help induce early osteogenesis. Composite hydrogels were analysed using Fourier transform infra-red spectroscopy, scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy, and rheology. Hydrogels with MBG showed a slightly rougher morphology upon SEM analysis. Composites containing 5% MBG and 2% FNPs showed good rheological properties, injectability, temperature stability, biomineralization and protein adsorption. Human umbilical vein endothelial cells (HUVECs) and rabbit-adipose derived mesenchymal stem cells (rASCs) were used for cyto-compatibility studies. Composite gels with 2% FNPs and 2% MBG (composite 1) were considered to be non-toxic to both the cells and were taken for further in vitro studies. Aortic ring assay was carried out to study the angiogenic potential of the hydrogels. The aorta placed with composite hydrogels showed enhanced sprouting of blood vessels. rASCs too showed good spreading on the composite hydrogels. Hydrogels containing MBG showed early initiation of differentiation and higher expression of alkaline phosphatase and osteocalcin confirming the osteoinductive property of MBG. These studies indicate that this composite hydrogel can be used for regenerating irregular bone defects.</p>

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2016

Journal Article

J. Perayil, Menon, K. S., Biswas, R., Fenol, A., and Vyloppillil, R., “Comparison of the efficacy of subgingival irrigation with 2% povidone-iodine and tetracycline HCl in subjects with chronic moderate periodontitis: A clinico microbiological study.”, Dent Res J (Isfahan), vol. 13, no. 2, pp. 98-109, 2016.[Abstract]


<p><b>BACKGROUND: </b>This study was performed to evaluate and compare the clinical and antimicrobial efficacy of subgingival irrigation with tetracycline and povidone-iodine as an adjunct to nonsurgical periodontal therapy.</p><p><b>MATERIALS AND METHODS: </b>Twenty subjects with chronic moderate periodontitis were recruited in this split-mouth study with probing pocket depth of >3 and ≤5 mm and clinical attachment loss of 3-4 mm in relation to 16, 36, and 46. In each subject, three selected periodontal pockets were assigned to receive one out of three irrigants (1) sterile water (control) in 16; (2) tetracycline at 10 mg/ml in 36; (3) 2% povidone-iodine in 46, and these sites were designated as Group A, Group B, and Group C, respectively. Plaque score, gingival score, pocket probing depth, and clinical attachment level were evaluated before treatment and at 1 and 3 months posttreatment. Multiplex polymerase chain reaction was used to detect Porphyromonas gingivalis and Tannerella forsythensis which have been implicated as the major risk factors for periodontal disease. Subgingival plaque collected before treatment and at 1 and 3 months posttreatment. Data were analysed using ANOVA and repeated measure ANOVA. Results were considered significant if P < 0.05.</p><p><b>RESULTS: </b>Clinical and microbiological parameters were reduced posttreatment, the reduction being significantly higher in Group B compared to Group C.</p><p><b>CONCLUSION: </b>It can be concluded that chemical and mechanical therapies were of slight benefit in the treatment of chronic moderate periodontitis, and there was an adjunctive effect of significance when scaling and root planing was combined with a single subgingival irrigation with tetracycline or povidone-iodine in lower concentration.</p>

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2016

Journal Article

N. Rajendran, Jayakumar, R., and Bumgardner, J. D., “Editorial.”, J Biomed Mater Res B Appl Biomater, vol. 104, no. 4, pp. 663-4, 2016.

2016

Journal Article

Mab Dangate, Munshi, Ab, Sampath, W. Sb, Boltalina, O. Vc, Strauss, S. Hc, Saravanan, Ca, and Shantikumar V Nair, “Investigation of Organic Small Molecules and Polymer Compounds for CdTe back Contact”, Conference Record of the IEEE Photovoltaic Specialists Conference, vol. 2016-November, pp. 1438-1442, 2016.[Abstract]


Different organic compounds are evaluated to form back contact for CdTe photovoltaics (PV) and to study the effect of band alignment. CdTe devices with CdS n-type window layer were fabricated using closed space sublimation (CSS) and organic back contact layers were deposited using dip coating. In order to prepare photovoltaic devices, the appropriate deposition parameters and thicknesses of organic compounds were selected experimentally. The best results were obtained with dip coated PEDOT-PSS aqueous dispersion with high electrical conductivity. The performance of devices with organic back contacts are compared to those with baseline CdTe devices with reduced copper doping.

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2016

Journal Article

R. Vilangattu Kunjikuttan, Jayasree, A., Biswas, R., and Jayakumar, R., “Recent developments in drug-eluting dressings for the treatment of chronic wounds.”, Expert Opin Drug Deliv, vol. 13, no. 12, pp. 1645-1647, 2016.

2016

Journal Article

R. Babu, Kumar, A., Karim, S., Warrier, S., Nair, S. G., Singh, S. K., and Biswas, R., “Faecal carriage rate of extended-spectrum β-lactamase-producing Enterobacteriaceae in hospitalised patients and healthy asymptomatic individuals coming for health check-up.”, J Glob Antimicrob Resist, vol. 6, pp. 150-153, 2016.[Abstract]


<p>The prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) in hospitalised and community patients is of significant public health concern. The aim of this study was to estimate the faecal carriage rate of ESBL-PE in hospitalised patients and healthy asymptomatic individuals coming for health check-up. Non-repetitive, consecutive stool samples from 480 adults (260 healthy individuals and 220 hospitalised patients) aged ≥18 years from November 2011 to July 2013 were screened using MacConkey agar supplemented with ceftazidime. All screen-positive isolates were identified to species level and were tested for ESBL production. Representative ESBL-PE isolates were subjected to susceptibility testing and multiplex ESBL PCR. The faecal carriage rate of ESBL-PE was found to be 62.7% among hospitalised patients and 33.8% among healthy asymptomatic individuals. The most common ESBL-PE was Escherichia coli (70.3% and 78.4% in hospitalised patients and healthy individuals, respectively), followed by Klebsiella pneumoniae (26.8% and 17.0%). ESBL-PE showed the highest sensitivity to carbapenems (85% and 100%, respectively), followed by amikacin (67.2% and 98%), cefoperazone/sulbactam (27.8% and 88.2%) and piperacillin/tazobactam (18% and 74.5%). Ciprofloxacin exhibited a high level of resistance among both groups. Molecular analysis for ESBL genes showed a predominance of the CTX-M gene. In conclusion, the faecal carriage rate of ESBL-PE among hospitalised patients was almost double that of healthy individuals. Carriage of carbapenem-resistant isolates is emerging among hospitalised patients. The spread of these organisms in the community merits radical measures to improve sanitation and implement antibiotic stewardship.</p>

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2016

Journal Article

S. Patil, Tyagi, A., Jose., J., Krishnakumar N. Menon, and Dr. Gopi Mohan C., “Integration of Common Feature Pharmacophore Modeling and in Vitro Study to Identify Potent AChE Inhibitors”, Medicinal Chemistry Research, vol. 25, pp. 2965–2975, 2016.[Abstract]


Alzheimer's disease is a progressive neurodegenerative disorder arising due to genetic and non-genetic causes. One of the major therapies adapted for symptomatic Alzheimer's disease is by targeting acetylcholinesterase enzyme based on the cholinergic hypothesis. Acetylcholinesterase is a substrate-specific enzyme that degrades the neuro-transmitter acetylcholine. An optimum level of acetylcholine should be maintained in the brain for its proper function. In order to identify potent and selective acetylcholinesterase inhibitors we adopted an integrated in silico and bioassay methodologies. In silico approach involves creating chemical features based 3D-pharmacophore models using AChE specific inhibitors. This model was then used for sequential virtual screening from the small molecule databases. Finally, five molecules were selected on the basis of the best docking scores and pharmacokinetics properties. These molecules were subjected to docking analysis with the recently solved crystal structure of human acetylcholinesterase enzyme, in order to reveal its binding mode and interactions at the dual binding sites of the enzyme. The acetylcholinesterase enzyme inhibitory activity of these five lead molecules was further assessed by in-vitro analysis.

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2016

Journal Article

T. R. Nimal, Baranwal, G., Bavya, M. C., Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Anti-staphylococcal Activity of Injectable Nano Tigecycline/Chitosan-PRP Composite Hydrogel Using Drosophila melanogaster Model for Infectious Wounds”, ACS Applied Materials and Interfaces, vol. 8, pp. 22074-22083, 2016.[Abstract]


Compared to the current treatment modalities, the use of an injectable hydrogel system, loaded with antibiotic encapsulated nanoparticles for the purpose of treating Staphylococcus aureus (S. aureus) chronic wound infections have several advantages. These include adhesiveness to infection site, reduced frequency of dressings, sustained drug release, inhibition of bacterial growth, and increased healing. In the present work tigecycline nanoparticles were loaded into chitosan-platelet-rich plasma (PRP) hydrogel. The tigecycline nanoparticles (95 ± 13 nm) were synthesized through ionic cross-linking method using chitosan, tripolyphosphate, and tigecycline and characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FT-IR). The synthesized nanoparticles and activated PRP powder were mixed with chitosan hydrogel to form a homogeneous gel. Rheology studies have confirmed the shear thinning property, thermal stability, and injectability of the prepared gel systems. The gel system was further assessed for its drug release property and found that it was released in a sustained manner. Hemolysis and blood-clotting assays demonstrated that the gel system was neither a hemolysin nor a hamper to the clotting cascade. Cell viability results showed that these nanoparticles were cyto-compatible. The bioactivity of PRP loaded chitosan gel toward fibroblast cell line was studied using cell proliferation and migration assay. In vitro antibacterial studies revealed that the gel system inhibited bacterial growth to a great extent. The antibacterial activity was further analyzed using ex vivo porcine skin assay. In vivo anti-Staphylococcal activity of the prepared hydrogels was studied using a Drosophila melanogaster infection model. The tigecycline and tigecycline nanoparticle incorporated chitosan gel showed a significant antibacterial activity against S. aureus. Thus, the gel system is an effective medium for antibiotic delivery and can be applied on the infection sites to effectively forestall various skin infections caused by S. aureus. © 2016 American Chemical Society.

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2016

Journal Article

S. Deepthi, M Sundaram, N., J Kadavan, D., and Jayakumar, R., “Layered chitosan-collagen hydrogel/aligned PLLA nanofiber construct for flexor tendon regeneration.”, Carbohydr Polym, vol. 153, pp. 492-500, 2016.[Abstract]


<p>The aim of our study was to develop a tendon construct of electrospun aligned poly (l-lactic acid) (PLLA) nanofibers, to mimic the aligned collagen fiber bundles and layering PLLA fibers with chitosan-collagen hydrogel, to mimic the glycosaminoglycans of sheath ECM for tendon regeneration. The hydrogel coated electrospun membrane was rolled and an outer coating of alginate gel was given to prevent peritendinous adhesion. The developed constructs were characterized by SEM, FT-IR and tensile testing. Protein adsorption studies showed lower protein adsorption on coated scaffolds compared to uncoated scaffolds. The samples were proven to be non-toxic to tenocytes. The chitosan-collagen/PLLA uncoated scaffolds and alginate gel coated chitosan-collagen/PLLA scaffolds showed good cell proliferation. The tenocytes showed good attachment and spreading on the scaffolds. This study indicated that the developed chitosan-collagen/PLLA/alginate scaffold would be suitable for flexor tendon regeneration. </p>

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2016

Journal Article

T. Gandhi, Melge, A. R., and C Mohan, G., “ identification of T-type calcium channel blockers: A ligand-based pharmacophore mapping approach.”, J Adv Res, vol. 7, no. 6, pp. 931-944, 2016.[Abstract]


<p>Limited progress has been made in the quest to identify both selective and non-toxic T-type calcium channel blocking compounds. The present research work was directed toward slaking the same by identifying the selective three dimensional (3D) pharmacophore map for T-type calcium channel blockers (CCBs). Using HipHop module in the CATALYST 4.10 software, both selective and non-selective HipHop pharmacophore maps for T-type CCBs were developed to identify its important common pharmacophoric features. HipHop pharmacophore map of the selective T-type CCBs contained six different chemical features, namely ring aromatic (R), positive ionizable (P), two hydrophobic aromatic (Y), hydrophobic aliphatic (Z), hydrogen bond acceptor (H) and hydrogen bond donor (D). However, non-selective T-type CCBs contain all the above mentioned features except ring aromatic (R). The present ligand-based pharmacophore mapping approach could thus be utilized in classifying selective vs. non-selective T-type CCBs. Further, the model can be used for virtual screening of several small molecule databases.</p>

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2016

Journal Article

S. Vijayrajratnam, Pushkaran, A. Choorakott, Balakrishnan, A., Vasudevan, A. Kumar, Biswas, R., and Mohan, C. Gopi, “Bacterial peptidoglycan with amidated meso-diaminopimelic acid evades NOD1 recognition: an insight into NOD1 structure-recognition.”, Biochem J, vol. 473, no. 24, pp. 4573-4592, 2016.[Abstract]


<p>Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an intracellular pattern recognition receptor that recognizes bacterial peptidoglycan (PG) containing meso-diaminopimelic acid (mesoDAP) and activates the innate immune system. Interestingly, a few pathogenic and commensal bacteria modify their PG stem peptide by amidation of mesoDAP (mesoDAP). In the present study, NOD1 stimulation assays were performed using bacterial PG containing mesoDAP (PG) and mesoDAP (PG) to understand the differences in their biomolecular recognition mechanism. PG was effectively recognized, whereas PG showed reduced recognition by the NOD1 receptor. Restimulation of the NOD1 receptor, which was initially stimulated with PG using PG, did not show any further NOD1 activation levels than with PG alone. But the NOD1 receptor initially stimulated with PG responded effectively to restimulation with PG The biomolecular structure-recognition relationship of the ligand-sensing leucine-rich repeat (LRR) domain of human NOD1 (NOD1-LRR) with PG and PG was studied by different computational techniques to further understand the molecular basis of our experimental observations. The d-Glu-mesoDAP motif of GMTP, which is the minimum essential motif for NOD1 activation, was found involved in specific interactions at the recognition site, but the interactions of the corresponding d-Glu-mesoDAP motif of PG occur away from the recognition site of the NOD1 receptor. Hot-spot residues identified for effective PG recognition by NOD1-LRR include W820, G821, D826 and N850, which are evolutionarily conserved across different host species. These integrated results thus successfully provided the atomic level and biochemical insights on how PGs containing mesoDAP evade NOD1-LRR receptor recognition.</p>

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2016

Journal Article

A. Mohan, Shantikumar V Nair, and Lakshmanan, V. - K., “Leucas aspera Nanomedicine Shows Superior Toxicity and Cell Migration Retarded in Prostate Cancer Cells”, Applied Biochemistry and Biotechnology, pp. 1-13, 2016.[Abstract]


Prostate cancer is one of the most common malignancies among men worldwide. The main aim of the present work was to clarify the advantages of a nanoformulation of ayurvedic herbal plants. Specifically, we assessed the improved anticancer activity of Leucas aspera nanoparticles compared with methanolic crude extract in PC3 prostate cancer cells and normal cells. L. aspera is a plant that is used in ayurveda due to the antirheumatic, antipyretic, anti-inflammatory, antibacterial, anticancer, and cytotoxic activities. Nanoparticles of L. aspera were prepared from plant methanolic extracts. Cytotoxic effect was studied in the normal and prostate cancer cells. Size and morphology of the formulated nanoparticles was assessed using dynamic light scattering and scanning electron microscopy. In vitro cytotoxicity of L. aspera nanoparticles for PC3 cells was concentration- and time-dependent. In vitro hemolysis assay, cellular uptake studies, cell aggregation studies, and cell migration assay established the anticancerous activity of L. aspera in prostate cancer. More »»

2016

Journal Article

C. S. Keechilot, Shenoy, V., Kumar, A., Dr. Lalitha Biswas, Vijayrajratnam, S., Dinesh, K., and Dr. Prem Kumar Nair, “Detection of Occult Hepatitis B and Window Period Infection Among Blood Donors by Individual donation Nucleic Acid Testing in a Tertiary Care Center in South India”, Pathogens and Global Health, pp. 1-5, 2016.[Abstract]


With the introduction of highly sensitive hepatitis B surface antigen immunoassay, transfusion associated HBV infection have reduced drastically but they still tend to occur due to blood donors with occult hepatitis B infection (OBI) and window period (WP) infection. Sera from, 24338 healthy voluntary blood donors were screened for HBsAg, HIV and HCV antibody using Vitros Enhanced Chemiluminescent Immunoassay. The median age of the donor population was 30 (range 18–54) with male preponderance (98%). All serologically negative samples were screened by nucleic acid testing (NAT) for viral DNA and RNA. NAT-positive samples were subjected to discriminatory NAT for HBV, HCV, and HIV and all samples positive for HBV DNA were tested for anti-HBc, anti-HBs, HBeAg. Viral load was determined using artus HBV RG PCR Kit. Of the 24,338 donors screened, 99.81% (24292/24338) were HBsAg negative of which NAT was positive for HBV DNA in 0.0205% (5/24292) donors. Four NAT positive donors had viral load of &lt;200&nbsp;IU/ml making them true cases of OBI. One NAT positive donor was negative for all antibodies making it a case of WP infection. Among OBI donors, 75% (3/4) were immune and all were negative for HBeAg. Precise HBV viral load could not be determined in all (5/5) NAT positive donors due to viral loads below the detection limit of the artus HBV RG PCR Kit. The overall incidence of OBI and WP infections was found to be low at 1 in 6503 and 1 in 24214 donations, respectively. More studies are needed to determine the actual burden of WP infections in Indian blood donors.

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2016

Journal Article

V. H. Somasundaram, Pillai, R., Malarvizhi, G., Anusha Ashokan, Gowd, S., Peethambaran, R., Palaniswamy, S., Unni, A. K. K., Nair, S., and Dr. Manzoor K., “Biodegradable Radiofrequency Responsive Nanoparticles for Augmented Thermal Ablation Combined with Triggered Drug Release in Liver Tumors”, ACS Biomaterials Science and Engineering, vol. 2, pp. 768-779, 2016.[Abstract]


Radiofrequency ablation (RFA) and doxorubicin (Dox) chemotherapy are separately approved for liver cancer therapy; however, both have limited success in the clinic due to suboptimal/nonuniform heating and systemic side effects, respectively. Here, we report a biodegradable nanoparticle (NP) system showing excellent RF hyperthermic response together with the ability to locally deliver Dox in the liver under RF trigger and control. The nanosystem was prepared by doping a clinically permissible dose (∼4.3 wt %, 0.03 ppm) of stannous ions in alginate nanoparticles (∼100 nm) coloaded with Dox at ∼13.4 wt % concentration and surface conjugated with galactose for targeting asialo-glycoprotein receptors in liver tumors. Targeted NP-uptake and increased cytotoxicity when combined with RF exposure was demonstrated in HEPG2 liver cancer cells. Following in vitro (chicken liver phantom) demonstration of locally augmented RF thermal response, in vivo scintigraphic imaging of 99Tc-labeled NPs was performed to optimize liver localization in Sprague-Dawley (SD) rats. RF ablation was performed in vivo using a cooled-tip probe, and uniformly enhanced (∼44%) thermal ablation was demonstrated with magnetic resonance imaging along with RF-controlled Dox release. In orthotopic rat liver tumor models, real-time infrared imaging revealed significantly higher (∼20 °C) RF thermal response at the tumor site, resulting in uniform augmented ablation (∼80%) even at a low RF power exposure of 15 W for just 1 min duration. Being a clinically acceptable, biodegradable material, alginate nanoparticles hold strong translational potential for augmented RF hyperthermia combined with triggered drug release.

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2016

Journal Article

R. Jayakumar, “Biological macromolecules for tissue regeneration.”, Int J Biol Macromol, vol. 93, no. Pt B, p. 1337, 2016.

2016

Journal Article

S. Suresh, Deepak, T. Gangadhara, Ni, C., Dr. Sreekala C. O., Satyanarayana, M., A. Nair, S., and Pillai, V. Pappukkuty, “The Role Of Crystallinity Of The Nb2O5 Blocking Layer On The Performance Of Dye-Sensitized Solar”, New Journal of Chemistry, vol. 40, 7 vol., pp. 6228-6237, 2016.[Abstract]


The prevention of back electron transfer by inserting an energy barrier layer at the interface of a photo-anode is an effective method for improving the photovoltaic parameters in dye sensitised solar cells (DSSCs). In this study, phase a modified Nb2O5 blocking layer was inserted at the fluorine doped tin oxide (FTO)/TiO2 interface via a Rf magnetron sputtering process. For a critical tunnelling distance of ∼40 nm, the crystalline Nb2O5 blocking layer improved the efficiency close to 7% and outperformed the amorphous blocking layer by about 68%. The longer electron lifetime observed in DSSCs containing an inhomogeneous Nb2O5 layer indicates that trapping/de-trapping impedes the discharge of electrons to the TiO2 band edge. The origin of the longer electron lifetime is explained by formulating a theory from photovoltage decay measurements.

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2016

Journal Article

R. Anney Matthew, Minsha Mallika Gopi, Menon, P., Dr. Jayakumar Rangasamy, and Dr. Lakshmi Sumitra, “Synthesis of Electrospun Silica Nanofibers for Protein/DNA Binding”, Materials Letters, vol. 184, pp. 5 - 8, 2016.[Abstract]


Silica is widely used as the nanomaterial carrier for DNA or protein delivery because of ease and multitude of methods for its synthesis and relatively simple ways with which its surface chemistry can be modified. In the present study, electrospun nano scale silica fibrous mats with diameters in the range of 250–320nm were synthesized using TEOS (Tetra ethyl ortho silicate) as a silica precursor along with Poly (vinyl pyrolidine) (PVP). These fibrous mats were used for effective binding/elution of plasmid DNA and BSA (Bovine Serum Albumin) under optimal conditions, which were demonstrated utilizing this combination of electrospun silica precursor and PVP. These silica fiberous mats are easier to control than silica nanoparticles and require less hazardous preparation than nanosheets developed via etching. The developed nanosilica mats could be a cost effective tool for DNA and protein delivery for different biotechnological and medical applications

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2016

Journal Article

S. K.S., V.-K., L., and Shantikumar V Nair, “Sustained Release of Rottlerin Encapsulated within Poly(D, L-lactic-co-glycolic acid) Nanoparticles Inhibits Migration and Clonogenicity in Pancreatic cancer Cells”, Journal of Nanoscience and Nanotechnology, vol. 16, 2016.[Abstract]


In our present study, we focused on the preparation and evaluation of a stable nano-formulation of small molecule drug rottlerin encapsulated within PLGA (Poly(D, L-lactic-co-glycolic acid)) nanoparticles. The endeavor was to increase therapeutic efficacy of rottlerin against, and drug delivery to, pancreatic cancer cells. Size and morphology analysis by Dynamic light scattering (DLS) and Scanning electron microscopy (SEM) revealed the average size of nanoparticles prepared was 150–300 nm. In vitro drug release study confirmed the suitability of PLGA nanoparticles as a matrix for controlled release of rottlerin. In vitro cytotoxicity assay in MiaPaCa-2 cells showed dose dependent and preferential toxicity on pancreatic cancer cells compared to normal Vero cells. Furthermore, apoptosis mediated cell death was higher in the rottlerin nanoparticles treated cells and there was also a significant delay in cancer cell migration along with reduction in colony formation. Henceforth the study prospects that the potential therapeutic value of rottlerin against pancreatic cancer can have added advantage through its nanoformulation using a suitable polymeric carrier.

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2016

Journal Article

G. E. Unni, Sasi, S., and A. Nair, S., “Higher Open-circuit Voltage Set by Cobalt Redox Shuttle in SnO2 Nanofibers-Sensitized CdTe Quantum Dot Solar Cells”, Journal of Energy Chemistry, vol. 25, pp. 481 - 488, 2016.[Abstract]


In this study, we report an efficient CdTe-SnO2 quantum dot (QD) solar cell fabricated by heat-assisted drop-casting of hydrothermally synthesized CdTe QDs on electrospun SnO2 nanofibers. The as-prepared QDs and SnO2 nanofibers were characterized by dynamic light scattering (DLS), UV–Vis spectroscopy, photoluminescence (PL) spectra, X-ray diffraction (XRD) and transmission electron microscopy (TEM). The SnO2 nanofibers deposited on fluorine-doped tin oxide (SnO2) and sensitized with the CdTe QDs were assembled into a solar cell by sandwiching against a platinum (Pt) counter electrode in presence of cobalt electrolyte. The efficiency of cells was investigated by anchoring QDs of varying sizes on SnO2. The best photovoltaic performance of an overall power conversion efficiency of 1.10%, an open-circuit voltage (Voc) of 0.80V, and a photocurrent density (JSC) of 3.70mA/cm2 were obtained for cells with SnO2 thickness of 5–6µm and cell area of 0.25cm2 under standard 1 Sun illumination (100mW/cm2). The efficiency was investigated for the same systems under polysulfide electrolyte as well for a comparison.

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2016

Journal Article

D. Menon, Gopikrishna, J., Narayanan, D., and Shantikumar V. Nair, “Nanoparticles as Drug Delivery Vehicles for the Therapy of Inflammatory Disorders”, Handbook of Immunological Properties of Engineered Nanomaterials, pp. 477-516, 2016.[Abstract]


Abstract The ever-exploding scientific advancements in the field of nanotechnology have enabled its integration into biosciences and medicine. Such interdisciplinary approaches allow researchers to engineer novel tools for diagnosis, therapy, and prognosis of different clinical complications. One of the most successful nano-tools that have emerged in recent years are nano-drug delivery devices. The use of such nano-sized carriers to load therapeutic agents (drugs, vaccines, biomolecules, and enzymes) aid in overcoming their pharmacological and toxicological hurdles through site-specific and controlled drug delivery. This chapter is a comprehensive account on the recent developments in the delivery of anti-inflammatory drugs using nanocarriers. Here, various kinds and types of nanocarriers and their countless inherent and engineered properties which make them ideal for delivering anti-inflammatory drugs, and the special characteristics of inflammation and inflammatory cells and tissues, which make them vulnerable to these nano-tools, will be discussed. The potential active and passive targeting approaches using drug-loaded nanocarriers for various inflammatory disorders are also elaborated.

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2016

Journal Article

K. S., K.S., S., K.C., R., Shantikumar V Nair, and K., L. V., “Anti-Proliferative Effect of Tinospora cordifolia Nano Particles in Prostate Cancer Cells”, Journal of Bionanoscience, 2016.

2016

Journal Article

A. Sivashanmugam, R. Kumar, A., M. Priya, V., Nair, S. V., and Jayakumar, R., “Erratum : An Overview of Injectable Polymeric Hydrogels for Tissue Engineering”, European Polymer Journal, vol. 75, p. 538, 2016.

2016

Journal Article

G. E. Unni, Deepak, T. G., and A. Nair, S., “Fabrication of CdSe Sensitized SnO2 Nanofiber Quantum Dot Solar Cells”, Materials Science in Semiconductor Processing, vol. 41, pp. 370 - 377, 2016.[Abstract]


In the present study, we report a cost-effective quantum dot solar cells based on a combination of electrospinning and successive-ionic-layer-adsorption and reaction (SILAR) methods. CdSe nanocrystals are deposited on electrospun SnO2 nanofibers by SILAR method using CdCl2 as the cadmium source and Na2Se as selenium source. The as-prepared materials are characterized by spectroscopy and microscopy. CdSe deposited SnO2 electrodes are also characterized by spectroscopy and microscopy. Cells are fabricated with platinum (Pt)-sputtered FTO glasses used as the counter electrodes and polysulfide solution used as the electrolyte. The efficiency of the cells is studied for different number of SILAR cycles. Current density–voltage (J–V) measurements on a cell having CdSe deposition of 7 SILAR cycles and SnO2 coating area 0.25cm2 showed an overall power conversion efficiency of 0.29 % with a photocurrent density (JSC) of 5.32mA cm−2 and open circuit voltage (VOC) of 0.23V under standard 1Sun illumination of 100mWcm−2 (AM 1.5G conditions). This is improved by carefully coating SnO2 film without losing the structures. Also ZnS passivation layer is coated to obtain an improved efficiency of 0.48% with JSC of 4.68mAcm−2, and VOC of 0.43V

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2015

Journal Article

A. Mohandas, Anisha, B. S., Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Chitosan-hyaluronic acid/VEGF loaded fibrin nanoparticles composite sponges for enhancing angiogenesis in wounds”, Colloids and Surfaces B: Biointerfaces, vol. 127, pp. 105-113, 2015.[Abstract]


Reduced levels of endogenous growth factors and diminished angiogenesis are contributory factors for impaired wound healing in diabetic patients. Vascular endothelial growth factor (VEGF) is the most potent angiogenic growth factor which stimulates multiple phases of wound healing angiogenesis and thereby accelerates healing. The aim of this work was to develop chitosan-hyaluronic acid composite sponge incorporated with fibrin nanoparticles loaded with VEGF as a wound dressing for diabetic wounds. VEGF loaded fibrin nanoparticles (150-180. nm) were prepared and characterized which were then incorporated to the composite sponge. The prepared sponges were characterized by SEM and FT-IR. Porosity, swelling, biodegradation, mechanical properties and haemostatic potential of the sponges were also studied. Release of VEGF from the composite sponges was evaluated using ELISA kit. More than 60% of the loaded VEGF was released in three days. Cell viability and attachment studies of the composite sponges were evaluated using human dermal fibroblast (HDF) cells and human umbilical vein endothelial cells (HUVECs). HUVECs seeded on VEGF containing sponges showed capillary like tube formation which was absent in control sponges. The results suggest that the prepared chitosan-hyaluronic acid/VEGF loaded nanofibrin composite sponges (CHVFS) have potential to induce angiogenesis in wound healing.

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2015

Journal Article

A. S. Pillai, Rajagopalan, R., Joseph, J., Amruthalakshmi, A., Ajay, A., Shakir, I., Shantikumar V Nair, and Balakrishnan, A., “Mesoscopic Architectures of Co(OH)2 Spheres with an Extended Array of Microporous Threads as Pseudocapacitor Electrode Materials”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 470, pp. 280-289, 2015.[Abstract]


The present study demonstrates a low temperature hydrothermal route for the synthesis of α-cobalt hydroxide comprising of randomly arrayed nano strands in a three dimensional plane. These micro/nano hybrid structures were used as building blocks for processing high surface area supercapacitor electrodes. Surface area of these structures was measured to be  100m2g-1. The influence of surface morphology in three different electrolytes namely lithium hydroxide, sodium hydroxide and potassium hydroxide was analyzed. The influence of surface morphology on capacitance and internal resistance was also determined and explained on the basis of redox reactions in these electrolytes. Capacitance values as high as 1024Fg-1 was attained for these structures when employed as thin film electrodes with life extending to more than 5000 cycles. Inductively coupled plasma-atomic emission spectroscopy was used to determine the electrode dissolution in the given electrolyte and the observations were co-related with the cycling stability. Low self-discharge, high rate capability along with low cost makes them promising systems for supercapacitor applications. © 2015 Elsevier B.V.

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2015

Journal Article

A. J. Sivaram, Rajitha Panonnummal, Maya, S., Dr. Jayakumar Rangasamy, and Dr. Sabitha M., “Nanogels for Delivery, Imaging and Therapy”, Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2015.[Abstract]


Nanogels are hydrogels having size in nanoregime, which is composed of cross-linked polymer networks. The advantages of nanogels include stimuli-responsive nature, easy drug loading, and higher drug-loading capacity, physical stability, versatility in design, stability of entrapped drug, and controlled release of the anti-inflammatory, antimicrobial, protein, peptide and anticancer drugs. Stimuli-responsive nature of nanogel is of particular importance in anticancer and anti-inflammatory drug delivery, as cancer and inflammation are associated with acidic pH, heat generation, and change in ionic content. Nanogels composed of muco-adhesive polymers provide prolonged residence time and increase the ocular availability of loaded drugs. By forming suitably sized complex with proteins or by acting as artificial chaperones, they thus help to keep the proteins and enzymes in proper confirmation necessary for exerting biological activity; nanogels can increase the stability and activity of protein/peptide drugs. Better drug penetrations achieved by prolonged contact with skin contribute much in transdermal drug delivery. When it comes to cancer drug delivery, the presence of multiple interactive functional groups in nanogels different targeting agents can be conjugated for delivery of the selective drugs. This review focuses on applications of nanogels in cancer drug delivery and imaging, anti-inflammatory, anti-psoriatic, transdermal, ocular and protein/peptide drug delivery and therapy.

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2015

Journal Article

N. S. Rejinold, Dr. Jayakumar Rangasamy, and Kim, Y. - C., “Radio Frequency Responsive Nano-biomaterials for Cancer Therapy”, Journal of Controlled Release, vol. 204, pp. 85-97, 2015.[Abstract]


Abstract Radiofrequency (RF)-assisted cancer therapy is well-known in the medical field as it is non-hazardous and can penetrate tissues, enabling a deeply rooted cancer treatment. However, the current treatment regimen is non-specific and invasive, making it difficult for patients to undergo the RF ablation procedure. Recently, there has been tremendous attention given on replacing RF probes (through which the RF current passes into the tumors) with metallic nanoparticles (NPs) such as gold and iron oxide. These metallic NPs can be combined with stimuli responsive polymers to have a simultaneous drug delivery to tumors and better thermal ablation. This review will give a brief overview on the various nanobiomaterials based on metals and polymers and their composites in RF-assisted cancer therapy. Special attention has been given on RF responsive composite nanomaterials. Besides these, the importance of RF-assisted drug delivery using the nanobiomaterials for cancer therapy, as well as the advantages and future perspectives of these materials are discussed in detail. © 2015 Elsevier B.V. All rights reserved.

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2015

Journal Article

Fa Mohammed, Manohar, Vb, Jose, Mc, Thapasum, AdFairozekha, Mohamed, Se, Shamaz, BfHalima, and D'Souza, Ng, “Estimation of copper in saliva and areca nut products and its correlation with histological grades of oral submucous fibrosis”, Journal of Oral Pathology and Medicine, vol. 44, pp. 208-213, 2015.[Abstract]


Background: The purpose of this study was to estimate the copper levels in saliva of patients with oral submucous fibrosis (OSF) and different areca nut products and its correlation with different histological grades of OSF. Methods: The study comprised 60 individuals, 30 OSF patients and 30 non-OSF individuals. Unstimulated whole saliva was collected, and copper analysis was performed using colorimetric method. The commercial areca nut products used by the patients were acquired and subjected to copper analysis through the atomic absorption spectrophotometer method. Oral biopsies were performed for OSF patients for histopathological correlation. Results: The mean salivary copper level was 27.023 μg/dl in OSF patients when compared with 8.393 μg/dl in non-OSF individuals (P < 0.005). The mean copper content in different areca nut products was 13.313 ppm (P < 0.005). Comparison of copper content in different areca nut products with salivary copper levels of OSF patients showed negative correlation (P < 0.853). Comparison of salivary copper levels between different histological grades of OSF yielded a statistically significant association between grades I and III (P < 0.005) and grades II and III OSF (P < 0.019). Comparison of copper content in areca nut products and different histological grades of OSF yielded weak negative statistical correlation (r = -0.116). Conclusion: Despite high copper content in areca nut products, the observations yielded a negative correlation with different histological grades of OSF. This further raises a doubt about the copper content in areca nut as an etiological factor for this crippling disease. © 2014 John Wiley and Sons A/S.

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2015

Journal Article

R. Ranjusha, Sonia, T. S., Lakshmi, V., Roshny, S., Kalluri, S., Kim, T. N., Shantikumar V Nair, and Balakrishnan, A., “Synthesis, Characterization and Rate Capability Performance of the Micro-porous MnO2 Nanowires as Cathode Material in Lithium Batteries”, Materials Research Bulletin, vol. 70, pp. 1-6, 2015.[Abstract]


A peculiar architecture of one-dimensional MnO<inf>2</inf> nanowires was synthesized by an optimized hydrothermal route and has been lucratively exploited to fabricate highly efficient microporous electrode overlays for lithium batteries. These fabricated electrodes comprised of interconnected nanoscale units with wire-shaped profile which exhibits high aspect ratio in the order of 102. Their outstanding intercalation/de-intercalation prerogatives have also been studied to fabricate lithium coin cells which revealed a significant specific capacity and power density of 251 mAh g-1 and 200 W kg-1, respectively. A detailed electrochemical study was performed to elucidate how surface morphology and redox reaction behaviors underlying these electrodes influence the cyclic behavior of the electrode. Rate capability tests at different C-rates were performed to evaluate the capacity and cycling performance of these coin cells. © 2015 Elsevier Ltd. All rights reserved.

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2015

Journal Article

N. Nair, Vinod, V., Suresh, M. K., Vijayrajratnam, S., Dr. Lalitha Biswas, Peethambaran, R., Vasudevan, A. K., and Dr. Raja Biswas, “Amidase, a Cell Wall Hydrolase, Elicits Protective Immunity Against Staphylococcus Aureus and S. Epidermidis”, International Journal of Biological Macromolecules, vol. 77, pp. 314-321, 2015.[Abstract]


The morbidity and the mortality associated with Staphylococcus aureus and S. epidermidis infections have greatly increased due to the rapid emergence of highly virulent and antibiotic resistant strains. Development of a vaccine-based therapy is greatly desired. However, no staphylococcal vaccine is available till date. In this study, we have identified Major amidase (Atl-AM) as a prime candidate for future vaccine design against these pathogens. Atl-AM is a multi-functional non-covalently cell wall associated protein which is involved in staphylococcal cell separation after cell division, host extracellular matrix adhesion and biofilm formation. Atl-AM is present on the surface of diverse S. aureus and S. epidermidis strains. When used in combination with Freund's adjuvant, Atl-AM generated a mixed Th1 and Th2 mediated immune response which is skewed more toward Th1; and showed increased production of opsonophagocytic IgG2a and IgG2b antibodies. Significant protective immune response was observed when vaccinated mice were challenged with S. aureus or S. epidermidis. Vaccination prevented the systemic dissemination of both organisms. Our results demonstrate the remarkable efficacy of Atl-AM as a vaccine candidate against both of these pathogens. © 2015 Elsevier B.V.

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2015

Journal Article

A. Paravannoor, Shantikumar V Nair, Pattathil, P., Manca, M., and Balakrishnan, A., “High Voltage Supercapacitors based on Carbon-Grafted NiO Nanowires Interfaced with an Aprotic Ionic Liquid”, Chemical Communications, vol. 51, pp. 6092-6095, 2015.[Abstract]


The report provides a preliminary assessment of the charge storage prerogatives of an asymmetric electrochemical capacitor employing a carbon-grafted NiO electrode interfaced with 1-ethyl-3-methyl imidazoliumdicyanamide as an ionic liquid electrolyte. This configuration has been demonstrated to be potentially exploited for developing hybrid supercapacitors providing as high energy density as 21 W h Kg-1.

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2015

Journal Article

A. G. Krishnan, Jayaram, L., Dr. Raja Biswas, and Dr. Manitha B. Nair, “Evaluation of antibacterial activity and cytocompatibility of ciprofloxacin loaded gelatin-hydroxyapatite scaffolds as a local drug delivery system for osteomyelitis treatment”, Tissue Engineering - Part A, vol. 21, pp. 1422-1431, 2015.[Abstract]


Surgical debridement of the dead bone and subsequent systemic antibiotic therapy is often ineffective in eliminating Staphylococcus aureus infections in osteomyelitic patients. The recurrence of S. aureus infection is mainly due to the intracellular growth of bacterial colonies within osteoblast cells that protect the organism from extracellular host defences and/or antibiotic therapy. In this study, porous gelatin-hydroxyapatite (HAP) scaffolds with various amounts of ciprofloxacin (1, 2, 5, and 10 wt%) were fabricated by freeze-drying technique and the release of the antibiotic was characterized, as was the efficacy of the released antibiotic against methicillin-sensitive and methicillin-resistant S. aureus. Furthermore, the impact of the released antibiotic on the viability and osteogenic differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) cultured on the scaffolds were assessed. Finally, the efficacy of the released ciprofloxacin to enter the cells and abate intracellularly located S. aureus was evaluated. All the groups of CGHA scaffolds displayed sustained release of ciprofloxacin against S. aureus for 60 days above the minimum inhibitory concentration for the target species with zero-order kinetics and Korsmeyer-Peppas models. While comparing, the released antibiotic from CGHA5 scaffolds was found to be effective at reducing S. aureus through the study period, without detrimental effects on human ADMSC viability or osteogenic potential. When stem cells internalized with S. aureus were cultured onto the drug-loaded scaffolds, a significant reduction in the colony count of internalized bacteria was observed, resulting in the osteogenic differentiation capability of those cells. Our results clearly demonstrate that the ciprofloxacin incorporated gelatin-HAP scaffolds, which were cytocompatible and could target both intracellular and extracellular S. aureus, defining its potential to be used as local drug delivery system. © Copyright 2015, Mary Ann Liebert, Inc. 2015.

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2015

Journal Article

D. Jaikumar, Sajesh, K. M., Soumya, S., Nimal, T. R., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Injectable Alginate-O-carboxymethyl Chitosan/nano Fibrin Composite Hydrogels for Adipose Tissue Engineering”, International Journal of Biological Macromolecules, vol. 74, pp. 318-326, 2015.[Abstract]


Injectable, biodegradable scaffolds are required for soft tissue reconstruction owing to its minimally invasive approach. Such a scaffold can mimic the native extracellular matrix (ECM), provide uniform distribution of cells and overcome limitations like donor site morbidity, volume loss, etc. So, here we report two classes of biocompatible and biodegradable hydrogel blend systems namely, Alginate/. O-carboxymethyl chitosan (O-CMC) and Alginate/poly (vinyl alcohol) (PVA) with the inclusion of fibrin nanoparticles in each. The hydrogels were prepared by ionic cross-linking method. The developed hydrogels were compared in terms of its swelling ratio, degradation profile, compressive strength and elastic moduli. From these preliminary findings, it was concluded that Alginate/. O-CMC formed a better blend for tissue engineering applications. The potential of the formed hydrogel as an injectable scaffold was revealed by the survival of adipose derived stem cells (ADSCs) on the scaffold by its adhesion, proliferation and differentiation into adipocytes. Cell differentiation studies of fibrin incorporated hydrogel scaffolds showed better differentiation was confirmed by Oil Red O staining technique. These injectable gels have potential in soft tissue regeneration. © 2014 Elsevier B.V.

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2015

Journal Article

A. Ajay, Paravannoor, A., Jipnomon Joseph, Amruthalakshmi, V., Anoop, S. S., Nair, S. V., and Balakrishnan, A., “2 D amorphous frameworks of NiMoO4 for supercapacitors: Defining the role of surface and bulk controlled diffusion processes”, Applied Surface Science, vol. 326, pp. 39-47, 2015.[Abstract]


<p>This study demonstrates a novel approach by which amorphous nickel molybdate nanoflakes were processed into high surface area electrodes for supercapacitors. Time dependent studies showed evolution of flake-like morphology from anisotropic nuclei particles exhibiting high redox activity. An intrinsic correlation between the surface area, specific capacitance and the internal resistance has been deduced and explained on the basis of relative contributions from the faradic reactions of NiMoO4. Relative contributions from the bulk and surface processes were mathematically modeled. The electrodes exhibited specific mass capacitance values as high as 1650 F g-1 which is the highest reported value so far. Coin cells employing these rechargeable electrodes were also demonstrated exhibiting an energy and power density of 92 W h kg-1 and 23 kW kg-1, respectively, with excellent cyclic stability. ©2014 Elsevier B.V. All rights reserved.</p>

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2015

Journal Article

A. M. Cherian, Snima, K. S., Kamath, C. R., Shantikumar V Nair, and Lakshmanan, V. K., “Effect of Baliospermum Montanum Nanomedicine Apoptosis Induction and Anti-migration of Prostate Cancer Cells”, Biomedicine and Pharmacotherapy, vol. 71, pp. 201-209, 2015.[Abstract]


Prostate cancer has been diagnosed as the second most frequent and the sixth among the cancer causing deaths among men worldwide. There is a limited scope for the prevalent therapies as prostate cancer advances and they present adverse aftermaths that have put way for us to delve into naturally available anticancer agents. The main objective of the present work is to compile the advantages of ayurvedic herbal formulations with modern technology. Baliospermum montanum is a plant that is used in ayurveda for the treatment of cancer and the plant is studied to possess various constituents in it that are responsible for its anticancer activity. Stable nanoparticles of B. montanum were prepared from both the aqueous and ethanolic extracts of the plant and its cytotoxic effects were studied on prostate cancer and normal cell lines. Size analysis by DLS and SEM revealed the average size of nanoparticles prepared was 100 ± 50. nm and 150 ± 50. nm for the nanoparticles prepared from aqueous and ethanolic extract respectively. In vitro cytotoxicity showed a concentration and time dependent toxicity on prostate cancer cells with cell viability of 22% and 6% with maximum concentration of aqueous and ethanolic nanoparticles respectively, in 48. h. In vitro hemolysis assay confirmed that the prepared nanoparticles were compatible with blood with no occurrence of hemolysis. The nanoparticles showed a significant reduction in the colony forming ability and wound healing capacity of the prostate cancer cells. These studies hold the anti cancer potential of the B. montanum nanoparticles making it an important candidate for prostate cancer therapy. © 2015 Elsevier Masson SAS.

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2015

Journal Article

K. H. Anupriya, Ranjusha, R., Shantikumar V Nair, Balakrishnan, A., and Subramanian, K. R. V., “Defining role of the Surface and Bulk Contributions in Camphoric Carbon Grafted Lithium Nickel Manganese Oxide Powders for Lithium ion Batteries”, Ceramics International, vol. 41, pp. 3269-3276, 2015.[Abstract]


In the present study, lithium nickel manganese oxide powders grafted with camphoric nano-carbons have been exploited to fabricate high voltage, high capacity rechargeable electrodes for Li storage. The prepared lithium nickel manganese oxide particles were pyrolyzed using a camphoric solution to graft porous camphoric carbon layer on to the surface. A detailed study was performed to elucidate the effect of carbon content on the performance of the electrode. Relative contributions of capacitive and diffusion-controlled processes underlying these composite electrodes have been mathematically modeled. The lithium nickel manganese oxide composites showed two times higher conductivity as compared to the pristine samples. These electrodes exhibited a specific capacity value of  154 mAhg-1 and showed good rate capability. The capacity fading was found to be  17% at the end of 200 cycles for 100% depth of discharge. The specific capacity and capacity retention for these blends were found to be  10% and  40% higher respectively than pristine powders which are promising considering their low cost and facile fabrication process. © 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

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2015

Journal Article

S. Nandan, Deepak, T. G., Nair, S. V., and Sreekumaran A Nair, “TiO2 nanofibers resembling 'yellow bristle grass' in morphology by a soft chemical transformation”, Dalton Transactions, vol. 44, pp. 9637-9645, 2015.[Abstract]


We synthesized a uniquely shaped one-dimensional (1-D) TiO2 nanostructure having the morphology of yellow bristle grass with high surface area by the titanate route under mild reaction conditions. The electrospun TiO2-SiO2 composite nanofibers upon treatment with concentrated NaOH at 80 °C under ambient pressure for 24 h resulted in sodium titanate (Na2Ti3O7) nanostructures. The Na2Ti3O7 nanostructures have an overall 1-D fibrous morphology but the highly porous fiber surfaces were decorated with layered thorn-like features (a morphology resembling that of yellow bristle grass) resulting in high surface area (113 m2 g-1) and porosity. The Na2Ti3O7 nanostructures were converted into TiO2 nanostructures of the same morphology by acidification (0.1 N HCl) followed by low temperature sintering (110°C) processes. Dye-sensitized solar cells (DSCs) constructed out of the material (cells of area 0.20 cm2 and thickness 12 μm) showed a power conversion efficiency (η) of 8.02% in comparison with commercial P-25 TiO2 (η = 6.1%). © The Royal Society of Chemistry 2015.

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2015

Journal Article

Y. Shengyuan, Sreekumaran A Nair, and Ramakrishna, S., “Morphology of the electrospun TiO2on the photovoltaic properties of CdS quantum dot-sensitized solar cells”, Journal of Nanoscience and Nanotechnology, vol. 15, pp. 721-725, 2015.[Abstract]


Various TiO2 building blocks i.e., spheres (S-TiO2), rods (R-TiO2), grains (G-TiO2) were produced by electrospinning technique and sensitized by CdS via successive ionic layer adsorption and reaction (SILAR) to investigate their morphological effect on the photovoltaic properties of quantum dot-sensitized solar cells (QDSCs). It was found that QDSCs with G-TiO2 achieved the highest overall conversion efficiency of 1.74% under one-sun AM1.5G illumination, which corresponds to an increase of ∼ 100% (0.87%) compared with S-TiO2 and ∼ 35% (1.29%) with R-TiO2, respectively. Electrochemical impedance spectroscopy shows a largest recombination resistance for G-TiO2 cells amongst the three which accounts for its superior photovoltaic performance. Copyright © 2015 American Scientific Publishers All rights reserved.

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2015

Journal Article

A. Sivashanmugam, R. Kumar, A., M. Priya, V., Nair, S. V., and Dr. Jayakumar Rangasamy, “An Overview of Injectable Polymeric Hydrogels for Tissue Engineering”, European Polymer Journal, 2015.[Abstract]


The desire and need to minimize traditional open surgeries is gearing up as it could reduce the healthcare expenses and improve the recovery time for the patients. Minimal invasive procedures using endoscopes, catheters and needles have been developed considerably in the last few decades. In the field of tissue engineering and regenerative medicine, there is a need for advancement over the conventional scaffolds and pre-formed hydrogels. In this scenario, injectable hydrogels have gained wider appreciation among the researchers, as they can be used in minimally invasive surgical procedures. Injectable gels with their ease of handling, complete filling of the defect area and good permeability have emerged as promising biomaterials. The system can effectively deliver a wide array of therapeutic agents like drugs, growth factors, fillers and even cells. This review provides an overview of the recent trends in the preparation of injectable hydrogels, along with key factors to be kept in balance for designing an effective injectable hydrogel system. Further, we have summarized the application of injectable hydrogels in adipose, bone, cartilage, intervertebral discs and muscle tissue engineering. © 2015 Elsevier Ltd.

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2015

Journal Article

Aa Vijayakumar, Rajagopalan, Rb, Sushamakumariamma, A. Sa, Joseph, Ja, Ajay, Aa, Nair, S. Va, Krishna, M. S. Da, and Balakrishnan, Aa, “Synergetic influence of ex-situ camphoric carbon nano-grafting on lithium titanates for lithium ion capacitors”, Journal of Energy Chemistry, vol. 24, pp. 337-345, 2015.[Abstract]


The present study provides detailed experimental results on the synthesis and characterization of carbonized lithium titanate spinel (LTO) composites as electrode materials for lithium ion capacitor. The LTO particles were grafted with a porous carbon layer obtained from the pyrolysis of camphor. The graphitic nature of the carbon was confirmed through Raman spectroscopy. The relative contributions from the capacitive and diffusion controlled processes underlying these electrodes were mathematically modeled. Electron transport mechanism underlying these electrodes was determined by measuring the work functions (φ) of LTO and carbon grafted LTO using ultraviolet photoelectron spectroscopy. These carbon grafted LTO composites exhibited an energy density of 330 mWh·L-1 and a peak power density of 2.8 kW·L-1, when employed as electrodes in coin cells with excellent cycling stability at the end of 4000 cycles. © 2015 Dalian Institute of Chemical Physics, the Chinese Academy of Sciences. Published by Elsevier B.V.

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2015

Journal Article

A. Anitha, Maya, S., Sivaram, A. J., Dr. Ullas Mony, and Dr. Jayakumar Rangasamy, “Combinatorial nanomedicines for colon cancer therapy”, Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2015.[Abstract]


<p>Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.</p>

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2015

Journal Article

O. M. Bhat, Kumar, P. U., Giridharan, N. V., Kaul, D., Kumar, M. J. M., and Dhawan, V., “Interleukin-18-induced atherosclerosis involves CD36 and NF-κB crosstalk in Apo E-/- mice”, Journal of Cardiology, vol. 66, pp. 28-35, 2015.[Abstract]


Objective: Interleukin (IL)-18 is a pleotropic cytokine involved in various inflammatory disorders. The transcription factor, nuclear factor kappa-B (NF-κB), is thought to play an important role in IL-18 signaling. The present study proposes a novel role for IL-18 in cholesterol efflux and plaque stability and demonstrates that pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor blocks IL-18 signaling in apolipoprotein (Apo) E-/- mice. Methods: Three groups of normal chow-diet-fed, male Apo E-/- mice, aged 12 weeks (n = 6/group) were employed: Gp I, PBS (2 mo); Gp II, recombinant (r)IL-18 (1 mo) followed by PBS (1 mo); Gp III, rIL-18 (1 mo) followed by PDTC (1 mo). Results: Significantly augmented expression of IL-18 receptor (R)α by fluorescence-activated cell sorting analysis and plasma IL-18 was observed in Gp II. There was a significant increase in total cholesterol and low-density lipoprotein cholesterol whereas high-density lipoprotein cholesterol was significantly decreased in Gp II. However, this pattern was reversed in Gp III. Significantly augmented mRNA expression of IL-18, CD36, matrix metalloproteinase (MMP)-9, and NF-κB was observed in Gp II but liver X receptor alpha (LXR-α) gene was significantly reduced. A significant increase in frequency of atherosclerotic lesions was observed in Gp II animals, whereas there was a significant decrease in the Gp III. Conclusion: IL-18 administration initiates inflammatory cascade by binding with IL-18 Rα via NF-κB which is involved in progression and destabilization of atherosclerotic plaques in Apo E-/- mice. This study also reveals that NF-κB blockade with PDTC, blocks IL-18 signaling through down-regulation of IL-18, IL-18 Rα, CD36, and MMP-9, thus reducing inflammation and restoring plaque instability via upregulation of LXR-α © 2014 Japanese College of Cardiology.

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2015

Journal Article

R. Sa Nair, Reshmi, Ta, Reshmi, Pb, Sarika, Ca, Snima, K. Sa, Akk, Ub, Nair, S. Va, Pavithran, Kc, Chennazhi, Ka, and Lakshmanan, V. - Ka, “Biocompatibility studies of pectin-fibrin nanocomposite bearing BALB/c mice”, Cellulose Chemistry and Technology, vol. 49, pp. 55-60, 2015.[Abstract]


Pectin is a natural polysaccharide and the pectin scaffold system has proved to be suitable for an intended use towards biomedical applications, such as drug delivery and tissue engineering. Studies on gemcitabine loaded pectin-fibrin scaffold have shown it to be cytotoxic towards ovarian cancer cells at the in vitro level. Our present study aims at substantiating the biocompatibility of the pectin-fibrin composite scaffold in a mouse implantation model in order to prove the compatibility of the scaffold system in vivo. Composite scaffolds were implanted and the biocompatibility was assessed after the 1st, 6th and 12th week of study, respectively. Macroscopic inspection of the implantation site revealed no pathological inflammatory responses and histopathology studies depicted remarkable neutrophil accumulation within the implant in a timely manner. Furthermore, the immune response indicated significant difference with cytokines IL-1β, IL-10, and IL-17α, respectively. These results suggested that this scaffold system could be a promising targeted drug delivery system for the slow release of drugs in a mouse disease model.

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2015

Journal Article

A. Mohandas, Nimal, T. R., Das, V., Dr. Sahadev Shankarappa, Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Drug Loaded Bi-layered Sponge for Wound Management in Hyperfibrinolytic Conditions”, Journal of Materials Chemistry B, vol. 3, pp. 5795-5805, 2015.[Abstract]


Excessive bleeding due to premature clot lysis and secondary bacterial wound infection are two significant problems that contribute to increased morbidity in patients with hyperfibrinolytic conditions. In this study, we have developed a bi-layered sponge that promotes fibrin clot stability and prevents secondary bacterial wound infections. Using the technique of freeze-drying, a bi-layer matrix consisting of hyaluronic acid (HA) containing aminocaproic acid (amicar) and chitosan containing tetracycline loaded O-carboxymethyl chitosan nanoparticles (Tet-O-CMC NPs) were produced. We hypothesized that the top chitosan layer with Tet-O-CMC NPs will prevent wound infection and concomitantly act as a matrix for cellular migration and subsequent wound healing, while the amicar-containing layer would promote clot stability. Tet-O-CMC NPs and bi-layer sponges were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM) and Fourier Transform Infra Red (FT-IR) spectroscopy. Physiochemical characterization such as porosity, swelling and mechanical testing was performed. The drug release study shows that the bi-layered sponge demonstrates a robust burst release of amicar and a sustained release of tetracycline. The ex vivo muscle permeation study indicated that Tet-O-CMC NPs have enhanced tissue permeation compared to free Tet. In vitro antibacterial activity of the bi-layer sponge towards laboratory and clinical strains of Staphylococcus aureus and Escherichia coli was proved. The ex vivo bacterial sensitivity study using porcine muscles confirmed the antibacterial activity, while the cell viability study using human dermal fibroblast (HDF) cells revealed its biocompatible nature. The in vitro antifibrinolytic study shows that the bi-layered sponge with amicar showed significant protection against streptokinase induced clot lysis. These studies suggest that the prepared amicar and tetracycline loaded chitosan-HA bi-layered sponge can be used effectively to promote better wound healing by simultaneously preventing bacterial infection, and enhancing clot stability. This journal is © The Royal Society of Chemistry 2015.

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2015

Journal Article

Jipnomon Joseph, Paravannoor, A., Shantikumar V Nair, Han, Z. J., Ostrikov, Kb, and Balakrishnan, A., “Supercapacitors based on camphor-derived meso/macroporous carbon sponge electrodes with ultrafast frequency response for ac line-filtering”, Journal of Materials Chemistry A, vol. 3, pp. 14105-14108, 2015.[Abstract]


Supercapacitor electrodes assembled from meso/macroporous camphor-derived carbon sponges show highly promising performance in ac line-filtering. The coin-type supercapacitor exhibits an ultrafast frequency response with a phase angle of -78°and a RC time constant of 319 μs at 120 Hz and may be a viable alternative to the presently dominant aluminium electrolytic capacitors. © The Royal Society of Chemistry 2015.

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2015

Journal Article

S. Narayanan, Dr. Ullas Mony, Vijaykumar, D. K., Dr. Manzoor K., Dr. Bindhu Paul, and Dr. Deepthy Menon, “Sequential release of epigallocatechin gallate and paclitaxel from PLGA-casein core/shell nanoparticles sensitizes drug-resistant breast cancer cells”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 11, pp. 1399-1406, 2015.[Abstract]


Nanomedicines consisting of combinations of cytotoxic drugs and molecular targeted therapeutics which inhibit specific downstream signals are evolving as a novel paradigm for breast cancer therapy. This research addresses one such combination of Paclitaxel (Ptx), having several adversities related to the activation of NF-κB pathway, with Epigallocatechin gallate (EGCG), a multiple signaling inhibitor, encapsulated within a targeted core/shell PLGA-Casein nanoparticle. The sequential release of EGCG followed by Ptx from this core/shell nanocarrier sensitized Ptx resistant MDA-MB-231 cells to Ptx, induced their apoptosis, inhibited NF-κB activation and downregulated the key genes associated with angiogenesis, tumor metastasis and survival. More importantly, Ptx-induced expression of P-glycoprotein was repressed by the nanocombination both at the protein and gene levels. This combination also offered significant cytotoxic response on breast cancer primary cells, indicating its translational value. From the Clinical Editor: Breast cancer is the most common cancer in women worldwide. As well as surgery, chemotherapy plays a major role in the treatment of breast cancer. The authors investigated in this article the combination use of a chemotherapeutic agent, Paclitaxel (Ptx), and an inhibitor of NF-?B pathway, packaged in a targeted nano-based delivery platform. The positive results provided a new pathway for future clinical use of combination chemotherapy in breast cancer. © 2015 Elsevier Inc.

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2015

Journal Article

J. Joseph, Shantikumar V Nair, and Dr. Deepthy Menon, “Integrating Substrateless Electrospinning with Textile Technology for Creating Biodegradable Three-Dimensional Structures”, Nano letters, vol. 15, pp. 5420–5426, 2015.[Abstract]


The present study describes a unique way of integrating substrateless electrospinning process with textile technology. We developed a new collector design that provided a pressure-driven, localized cotton-wool structure in free space from which continuous high strength yarns were drawn. An advantage of this integration was that the textile could be drug/dye loaded and be developed into a core–sheath architecture with greater functionality. This method could produce potential nanotextiles for various biomedical applications.

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2015

Journal Article

M. Janani, Srikrishnarka, P., Shantikumar V Nair, and Nair, A. S., “An in-depth review on the role of carbon nanostructures in dye-sensitized solar cells”, Journal of Materials Chemistry A, vol. 3, pp. 17914-17938, 2015.[Abstract]


Dye-sensitized solar cells (DSSCs) are considered to be promising, low-cost alternatives to amorphous silicon solar cells. The major components of a DSC include a metal oxide (usually TiO2), a dye, an electrolyte and a Pt- or carbon-deposited counter electrode. The photoexcited electrons from the dye diffuse through the TiO2 network and reach the counter electrode through an external circuit. However due to the trap-limited diffusion process, the electron collection efficiency is affected. Thus, for a hassle-free transport of electrons there is a need for additional electron transport channels. Further in order to reduce the overall cost of the device there is also a need for cheaper alternative counter electrodes in place of Pt. The 15th most abundant element in the earth's crust, carbon and its allotropes with their outstanding catalytic activity and electrical conductivity prove to be promising materials to overcome all these shortcomings and demerits. The review presented below summarizes the up-to-date research efforts on the role of carbon nanostructures in DSSCs, the various synthesis strategies adopted for their preparation and their photovoltaic performance. The review also includes a brief discussion about the role of carbon nanostructures in non-planar flexible wire-shaped DSSCs. © The Royal Society of Chemistry 2015.

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2015

Journal Article

Dr. Manitha B. Nair, Baranwal, G., Vijayan, P., Keyan, K. S., and Dr. Jayakumar Rangasamy, “Composite hydrogel of chitosan-poly(hydroxybutyrate-co-valerate) with chondroitin sulfate nanoparticles for nucleus pulposus tissue engineering”, Colloids and Surfaces B: Biointerfaces, vol. 136, pp. 84-92, 2015.[Abstract]


Intervertebral disc degeneration, occurring mainly in nucleus pulposus (NP), is a leading cause of low back pain. In seeking to mitigate this condition, investigators in the field of NP tissue engineering have increasingly studied the use of hydrogels. However, these hydrogels should possess appropriate mechanical strength and swelling pressure, and concurrently support the proliferation of chondrocyte-like cells. The objective of this study was to develop and validate a composite hydrogel for NP tissue engineering, made of chitosan-poly(hydroxybutyrate- co-valerate) (CP) with chondroitin sulfate (CS) nanoparticles, without using a cross linker. The water uptake ability, as well as the viscoelastic properties of this composite hydrogel, was similar to native tissue, as reflected in the complex shear modulus and stress relaxation values. The hydrogel could withstand varying stress corresponding to daily activities like lying down (0.01. MPa), sitting (0.5. MPa) and standing (1.0. MPa) under dynamic conditions. The hydrogels were stable in PBS for 2 weeks and its stiffness, elastic and viscous modulus did not alter significantly during this period. Both CP and CP-CS hydrogels could assist the viability and adhesion of adipose derived rat mesenchymal stem cells (ADMSCs). The viability and chondrogenic differentiation of MSCs was significantly enhanced in presence of CS nanoparticles. Thus, CS nanoparticles-incorporated chitosan-PHBV hydrogels offer great potential for NP tissue engineering. © 2015 Elsevier B.V.

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2015

Journal Article

G. J. Pillai, Greeshma, M. M., and Dr. Deepthy Menon, “Impact of poly(lactic-co-glycolic acid) nanoparticle surface charge on protein, cellular and haematological interactions”, Colloids and Surfaces B: Biointerfaces, vol. 136, pp. 1058-1066, 2015.[Abstract]


The initial interactions of nanoparticles with biomolecules have a great influence on its toxicity, efficacy, biodistribution and clearance. The present work is an attempt to understand the impact of surface charge of polymeric nanoparticles on its plasma protein and cellular interactions. Negative, near-neutral and positively charged poly(lactic-. co-glycolic acid) [PLGA] nanoparticles were prepared using casein, poly(vinyl alcohol) and poly(ethylene imine) respectively, as surface stabilizers. A significant temporal variation in the hydrodynamic diameter of PLGA nanoparticles was observed in the presence of plasma proteins, which correlated with the amount of proteins adsorbed to each surface. Positively charged particles displayed the maximum size variation and protein adsorption. Cellular uptake of differentially charged nanoparticles was also concurrent with the quantity of adsorbed proteins, though there was no significant difference in their cytotoxicity. Haematological interactions (haemolysis and plasma coagulation times) of positively charged nanoparticles were considerably different from near-neutral and negative nanoparticles. Collectively, the results point to the interplay between plasma protein adsorption and cellular interactions of PLGA nanoparticles, which is governed by its surface charge, thereby necessitating a rational design of nanoparticles. © 2015 Elsevier B.V.

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2015

Journal Article

P. Pillai, Surenya, R. S., Shantikumar V Nair, and Lakshmanan, V. - K., “Cancer kinases and its novel inhibitors: Past, present and future challenges”, Current Drug Targets, vol. 16, pp. 1233-1245, 2015.[Abstract]


Cancer kinome is now well organized as an important target for a new class of cancer drugs. There are more than 500 members in the kinase family in which some of them are clinically analysed, while the rest are under investigation for potential therapeutic applications. Phosphorylation, major function of kinases is one of the most significant signal transduction mechanism in which intercellular signals regulate intracellular processes like ion transport, hormone responses and cellular proliferation. Any deregulation of kinase function may lead to tumor progression and other disorders such as immu-nological, neurological, metabolic including also infectious diseases. This led to the necessity in the development of kinase inhibitors as therapeutic agent. Herein we discuss about different types of kinases and their inhibitors in various types of cancers. This review portrays a broad overview of the origin of kinases, discovery, the characterization and mode of action of kinase inhibitors in cancer therapy. © 2015 Bentham Science Publishers.

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2015

Journal Article

A. Y. Rwei, Lee, J. - J., Zhan, C., Liu, Q., Ok, M. T., Dr. Sahadev Shankarappa, Langer, R., and Kohane, D. S., “Repeatable and Adjustable on-demand Sciatic Nerve Block with Phototriggerable Liposomes”, Proceedings of the National Academy of Sciences, 2015.[Abstract]


Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.

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2015

Journal Article

A. G.S., T.G., D., S.V., N., and A.S., N., “Facile fabrication of TiO2 nanoparticle-TiO2 nanofiber composites by co-electrospinning-electrospraying for dye-sensitized solar cells”, Journal of Energy Chemistry, vol. 24, pp. 762-769, 2015.[Abstract]


We report a facile method for the fabrication of TiO2 nanofiber-nanoparticle composite (FP) via. simultaneous electrospraying and electrospinning for dye-sensitized solar cell (DSC) applications. The loading of nanoparticles on the fibers is controlled by varying their feed rates during electrospinning. The FP composites having three different particle loading are prepared by the methodology and the FP with the highest particle loading (denoted as FP-3 in the manuscript) showed the best overall efficiency of 9.15% in comparison to the other compositions of the FP (FP-2, 8.15% and FP-1, 7.51%, respectively) and nanofibers (F) and nanoparticles (P) separately (7.21 and 7.81, respectively). All the material systems are characterized by spectroscopy, microscopy, surface area measurements and the devices are characterized by current-voltage (I-V), incident photon-to-current conversion efficiency (IPCE), electrochemical impedance measurements, etc. I-V, dye-loading and reflectance measurements throw light on the overall performance of the DSC devices. © 2015 Science Press and Dalian Institute of Chemical Physics. All rights reserved.

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2015

Journal Article

V. Thi Trang, Rai, A. Kumar, Jihyeon, G., and Jaekook, K., “High performance of Co-doped NiO nanoparticle anode material for rechargeable lithium ion batteries”, Journal of Power Sources, vol. 292, pp. 23 - 30, 2015.[Abstract]


Abstract A comparative electrochemical study of undoped NiO and Co-doped NiO is performed in order to elucidate the effect of the Co distribution in the crystal lattice of NiO for energy storage applications. Both samples are synthesized using a facile solvothermal strategy and characterized systematically by X-ray diffraction, field-emission scanning electron microscopy, field-emission transmission electron microscopy, X-ray photoelectron spectroscopy and charge/discharge measurements. It is found that doping process does not affect the phase structure of pristine NiO. However, it obviously significantly influences the morphology, suppresses the particles agglomeration and enhances the specific surface area of NiO. More importantly, the substitution of Co for Ni site enhances the p-type conductivity of NiO via the generation of holes. Consequently, the obtained Co-doped NiO anode displays superior Li-battery performance with a large reversible capacity, excellent cyclic performance, and good rate capability in comparison to undoped NiO.

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2015

Journal Article

A. Kumar Rai, Thi, T. Vu, Gim, J., Kim, S., and Kim, J., “Li 3 V 2 (PO 4) 3/graphene nanocomposite as a high performance cathode material for lithium ion battery”, Ceramics International, vol. 41, pp. 389 - 396, 2015.[Abstract]


Abstract In this work, pure \{LVP\} nanoparticles and an LVP/graphene nanocomposite are successfully synthesized by a simple and cost effective polyol based solvothermal method, which can be easily scaled up. The synthesized nanocomposite contained small (30–60 nm) \{LVP\} nanoparticles completely and uniformly anchored on reduced graphene nanosheets. As a cathode for lithium ion batteries, the nanocomposite electrode delivered high reversible lithium storage capacity (189.8 mA h g−1 at 0.1 C), superior cycling stability (111.8 mA h g−1 at 0.1 C, 112.6 mA h g−1 at 5 C, and 103.4 mA h g−1 at 10 C after 80 cycles) and better C-rate capability (90.8 mA h g−1 at 10 C), whereas the pure \{LVP\} nanoparticles electrode delivered much less capacity at all investigated current rates. The enhanced electrochemical performance of the nanocomposite electrode can be attributed to the synergistic interaction between the uniformly dispersed \{LVP\} nanoparticles and the graphene nanosheets, which offers a large number of accessible active sites for the fast diffusion of Li ions, low internal resistance, high conductivity and more importantly, accommodates the large volume expansion/contraction during cycling.

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2015

Journal Article

M. Hilmy Alfaruqi, Rai, A. Kumar, Mathew, V., Jo, J., and Kim, J., “Pyro-Synthesis of Nanostructured Spinel ZnMn 2 O 4/C as Negative Electrode for Rechargeable Lithium-Ion Batteries”, Electrochimica Acta, vol. 151, pp. 558 - 564, 2015.[Abstract]


Abstract ZnMn2O4/C nanoparticles are synthesized by one step polyol assisted pyro-synthesis for use as the anode in rechargeable lithium ion batteries without any post heat treatment. The as-prepared ZnMn2O4/C is tetragonal with a spherical particle size in the range of 10–30 nm. Electrochemical measurements were performed using the as-prepared powders as the active material for a lithium-ion cell. The nanoparticle electrode delivered an initial charge capacity of 666.1 mAh g−1 and exhibited a capacity retention of ∼81% (539.4 mAh g−1) after 50 cycles. The capacity enhancement in the as-prepared ZnMn2O4/C may be explained on the basis of the polyol medium that enables to develop a sufficient carbon network that can act as electrical conduits during electrochemical reactions. The carbon network appears to enhance the particle-connectivity and hence improve the electronic conductivities.

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2015

Journal Article

Dr. Manitha B. Nair, Nancy, D., Krishnan, A. G., Anjusree, G. S., Vadukumpully, S., and Shantikumar V Nair, “Graphene oxide nanoflakes incorporated gelatin–hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells”, Nanotechnology, vol. 26, p. 161001, 2015.[Abstract]


In this study, graphene oxide (GO) nanoflakes (0.5 and 1 wt%) were incorporated into a gelatin–hydroxyapatite (GHA) matrix through a freeze drying technique and its effect to enhance mechanical strength and osteogenic differentiation was studied. The GHA matrix with GO demonstrated less brittleness in comparison to GHA scaffolds. There was no significant difference in mechanical strength between GOGHA 0.5 and GOGHA 1.0 scaffolds. When the scaffolds were immersed in phosphate buffered saline (to mimic physiologic condition) for 60 days, around 50–60% of GO was released in sustained and linear manner and the concentration was within the toxicity limit as reported earlier. Further, GOGHA 0.5 scaffolds were continued for cell culture experiments, wherein the scaffold induced osteogenic differentiation of human adipose derived mesenchymal stem cells without providing supplements like dexamethasone, L-ascorbic acid and β glycerophosphate in the medium. The level of osteogenic differentiation of stem cells was comparable to those cultured on GHA scaffolds with osteogenic supplements. Thus biocompatible, biodegradable and porous GO reinforced gelatin–HA 3D scaffolds may serve as a suitable candidate in promoting bone regeneration in orthopaedics.

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2015

Journal Article

S. Deepthi, Jeevitha, K., M Sundaram, N., Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Chitosan–Hyaluronic acid Hydrogel Coated Poly (caprolactone) Multiscale Bilayer Scaffold for Ligament Regeneration”, Chemical Engineering Journal, vol. 260, pp. 478–485, 2015.[Abstract]


Ligament tears, seen in young athletes to elderly people, pose a very challenging problem to achieve complete healing, due to its hypocellularity that decelerate regeneration of ligament after injury. Tissue engineering is an approach for the ligament regeneration that optimizes the response of cell-biomaterial interaction to fasten regeneration using engineered scaffolds that mimic the native environment. Electrospinning techniques and hydrogels are useful to engineer the structure of ligament. In this study, electrospun multiscale fibrous scaffold of PCL aligned microfibers/random nanofibers (PCL aligned multiscale fibers) and PCL random microfibers/nanofibers (PCL random multiscale fibers) were developed. Chitosan-hyaluronic acid hydrogel coating was done on these fibrous scaffolds and this was layered to form a bilayered construct. The developed scaffold was characterized by SEM, FTIR, and tensile testing. Protein adsorption studies show better protein adsorption on coated scaffolds compared to uncoated scaffolds which further improved the cell viability as determined by Alamar blue assay and DNA quantification by Pico green assay. Rabbit ligament fibroblast cell attachment and infiltration study conducted on the scaffolds showed cell elongation along the aligned fibers, which would be advantageous in the need to align cells along the direction of force in native ligament environment. Hydrogel coating on PCL random multiscale fibers show better cell infiltration. This study implies the use of hydrogel coated systems to provide a reservoir for cells and nutrients and further modifications of these systems would make it promising for ligament regeneration. © 2014 Elsevier B.V.

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2015

Journal Article

D. Narayanan, Nair, S., and Menon, D., “A systematic evaluation of hydroxyethyl starch as a potential nanocarrier for parenteral drug delivery”, International Journal of Biological Macromolecules, vol. 74, pp. 575-584, 2015.[Abstract]


Development of parenteral nanoformulations is highly challenging due to the stringent demands on stability, reproducibility and high drug loading with minimal excipients. This study focuses on the development of a pharmaceutically acceptable nanomatrix system for parenteral delivery based on Hydroxyethyl Starch (HES), a FDA approved polymer that is relatively unexplored in drug delivery research. HES nanoparticles were prepared through a simple, two-step crosslinking-precipitation route, yielding 160. ±. 5. nm, nearly monodispersed spherical particles with high colloidal stability. The utility of this nanocarrier for parenteral delivery was verified by a panel of hemo/cytocompatibility assays at high concentrations (0.05-1. mg/ml) in vitro and in vivo. HES nanomatrix was found effective in encapsulating two chemically distinct drugs having varying hydrophobicities, with the release behavior being influenced by their chemical nature and drug-matrix interactions. Better in vitro efficacy was measured for the nanoencapsulated drug than its bare form, establishing the potential of HES nanocarriers for controlled drug delivery. © 2014 Elsevier B.V.

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2015

Journal Article

V. Kiruthika, Maya, S., Suresh, M. K., V. Kumar, A., Dr. Jayakumar Rangasamy, and Dr. Raja Biswas, “Comparative Efficacy of cChloramphenicol Loaded Chondroitin Sulfate and Dextran Sulfate Nanoparticles to Treat Intracellular Salmonella Infections”, Colloids and Surfaces B: Biointerfaces, vol. 127, pp. 33-40, 2015.[Abstract]


Salmonella Paratyphi A is a food-borne Gram-negative pathogen and a major public health challenge in the developing world. Upon reaching the intestine, S. Paratyphi A penetrates the intestinal epithelial barrier; and infects phagocytes such as macrophages and dendritic cells. S. Paratyphi A surviving within macrophages is protected from the lethal action of antibiotics due to their poor penetration into the intracellular compartments. Hence we have developed chloramphenicol loaded chondroitin sulfate (CS-Cm Nps) and dextran sulfate (DS-Cm Nps) nanoparticles through ionotropic-gelation method for the intracellular delivery of chloramphenicol. The size of these nanoparticles ranged between 100 and 200. nm in diameter. The encapsulation efficiency of both the nanoparticles was found to be around 65%. Both the nanoparticles are found to be non-hemolytic and non-toxic to fibroblast and epithelial cells. The prepared nanoparticles exhibited sustained release of the drug of up to 40% at pH 5 and 20-25% at pH 7.0 after 168 h. The anti-microbial activities of both nanoparticles were tested under in vitro and ex vivo conditions. The delivery of DS-Cm Nps into the intracellular compartments of the macrophages was 4 fold more compared to the CS-Cm Nps which lead to the enhanced intracellular antimicrobial activity of Ds-Cm Nps. Enhanced anti-microbial activity of Ds-Cm Nps was further confirmed in an ex vivo chicken intestine infection model. Our results showed that Cm loaded DS Nps can be used to treat intracellular Salmonella infections. © 2015 Elsevier B.V.

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2015

Journal Article

S. Sasi, Murali, A., Nair, S. V., Nair, A. S., and Subramanian, K. R. V., “The effect of graphene on the performance of an electrochemical flow capacitor”, Journal of Materials Chemistry A, vol. 3, pp. 2717-2725, 2015.[Abstract]


The electrochemical flow capacitor (EFC) plays an important role in the energy storage field. The potential and ease of large scale energy storage of an EFC makes it highly adaptable for grid-scale energy storage. Current working models for an EFC operate with activated carbon and other coarse-sized carbon-based materials as the input slurry material with limited device performance. Graphene, which has a large specific surface area and also offers the advantage of being in the nano-carbon form, is an excellent candidate for energy storage. In this paper, we investigate the efficiency enhancement of an EFC device when a graphene nanoplatelets-ionic electrolyte was used as the input slurry material for the flow device and charged-discharged; moreover, we have compared it with the coarse and conventional graphite-aqueous electrolyte slurry. The performance evaluation of a newly developed composition of graphene-based slurry with high capacitance was carried out and this slurry was used as both static and dynamic energy storage device. Thin film layers coated with this slurry have a high electrode specific capacitance greater than 300 F g-1, low-cost and a nickel-free composition with relatively low toxicity. The intermittent flow device has shown a device capacitance of 64.5 F with 2 V and a 5 mL graphene slurry input, which corresponds to an energy density of 14.3 W h L-1. The device with a graphite slurry has shown a capacitance of 2.3 F with 1.6 V and an energy density of 0.422 W h L-1. When the graphene nanoplatelets-based slurry was used in the actual EFC full flow device, it gives a capacitance of 1.08 F, 2 V device performance with a slurry input of 24 mL. Moreover, the graphene nanoplatelets-based slurry when used together with the ionic electrolyte shows a better device EFC performance (i.e. an energy density of 6 W h kg-1 (0.064 W h L-1)) when compared to using a coarse graphite-based slurry (device capacitance of 0.75 F with 1.6 V, and an energy density of 2.2 W h kg-1 (0.026 W h L-1)). Thus, this proof-of-concept study gives a significant difference in performance between a graphene slurry-based device and the conventional graphite slurry-based device. This model can be extended further by slurry material modification (such as the addition of materials displaying faradaic capacitance) to realize better performing flow-based devices. This journal is © The Royal Society of Chemistry 2015.

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2015

Journal Article

K. T. Smitha, Nisha, N., Maya, S., Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Delivery of rifampicin-chitin nanoparticles into the intracellular compartment of polymorphonuclear leukocytes”, International Journal of Biological Macromolecules, vol. 74, pp. 36 - 43, 2015.[Abstract]


Abstract Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the \{PMNs\} protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of \{PMNs\} is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the \{PMNs\} and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350 ± 50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was ∼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5–6 fold enhanced delivery of \{RIF\} into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections. More »»

2015

Journal Article

A. C. Pushkaran, Nataraj, N., Nair, N., Götz, F., Dr. Raja Biswas, and Dr. Gopi Mohan C., “Understanding the Structure–Function Relationship of Lysozyme Resistance in Staphylococcus aureus by Peptidoglycan O-Acetylation Using Molecular Docking, Dynamics, and Lysis Assay”, Journal of Chemical Information and Modeling, vol. 55, pp. 760-770, 2015.[Abstract]


Lysozyme is an important component of the host innate defense system. It cleaves the β-1,4 glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine of bacterial peptidoglycan and induce bacterial lysis. Staphylococcus aureus (S. aureus), an opportunistic commensal pathogen, is highly resistant to lysozyme, because of the O-acetylation of peptidoglycan by O-acetyl transferase (oatA). To understand the structure–function relationship of lysozyme resistance in S. aureus by peptidoglycan O-acetylation, we adapted an integrated approach to (i) understand the effect of lysozyme on the growth of S. aureus parental and the oatA mutant strain, (ii) study the lysozyme induced lysis of exponentially grown and stationary phase of both the S. aureus parental and oatA mutant strain, (iii) investigate the dynamic interaction mechanism between normal (de-O-acetylated) and O-acetylated peptidoglycan substrate in complex with lysozyme using molecular docking and molecular dynamics simulations, and (iv) quantify lysozyme resistance of S. aureus parental and the oatA mutant in different human biological fluids. The results indicated for the first time that the active site cleft of lysozyme binding with O-acetylated peptidoglycan in S. aureus was sterically hindered and the structural stability was higher for the lysozyme in complex with normal peptidoglycan. This could have conferred reduced survival of the S. aureus oatA mutant in different human biological fluids. Consistent with this computational analysis, the experimental data confirmed decrease in the growth, lysozyme induced lysis, and lysozyme resistance, due to peptidoglycan O-acetylation in S. aureus.

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2015

Journal Article

B. Halima Shamaz, Anitha, A., Vijayamohan, M., Kuttappan, S., Nair, S., and Dr. Manitha B. Nair, “Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration”, Nanotechnology, vol. 26, no. 40, p. 405101, 2015.[Abstract]


Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)–polyvinyl alcohol (PVA) were incorporated into a gelatin–nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin–HA matrix. The incorporation of PLLA microfibers within the gelatin–nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

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2015

Journal Article

Dr. Manitha B. Nair and Elizabeth, E., “Applications of Titania Nanotubes in Bone Biology”, Journal of Nanoscience and Nanotechnology, vol. 15, pp. 939–955, 2015.[Abstract]


Orthopedic implants, including artificial joints and fracture fixation devices, have helped to restore the physical independence of many patients, thereby improving the quality of their lives. Titania (Ti) and its alloys are better implant materials than stainless steel and Co–Cr alloys owing to their superior mechanical properties and biocompatibility; however, Ti-based implants may sometimes fail, leading to repeated surgeries. With the recent advancements in nanotechnology, the nanosurface modifications of Ti, especially in the form of Ti nanotubes (TNTs), have drastically improved the properties of orthopedic implants. In this review, we have summarized the fabrication of Ti nanotubes by electrochemical anodization and their influence on osteoblast cells and staphylococcus aureus. In addition, we have discussed the corrosion resistance of Ti nanotubes.

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2015

Journal Article

A. M. Henslee, Yoon, D. M., Lu, B. Y., Yu, J., Arango, A. A., Marruffo, L. P., Seng, L., Anver, T. D., Ather, H., Dr. Manitha B. Nair, and , “Characterization of an injectable, degradable polymer for mechanical stabilization of mandibular fractures”, Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 103, pp. 529–538, 2015.[Abstract]


This study investigated the use of injectable poly(propylene fumarate) (PPF) formulations for mandibular fracture stabilization applications. A full factorial design with main effects analysis was employed to evaluate the effects of the PPF:N-vinyl pyrrolidone (NVP, crosslinking agent) ratio and dimethyl toluidine (DMT, accelerator) concentration on key physicochemical properties including setting time, maximum temperature, mechanical properties, sol fraction, and swelling ratio. Additionally, the effects of formulation crosslinking time on the mechanical and swelling properties were investigated. The results showed that increasing the PPF:NVP ratio from 3:1 to 4:1 or decreasing the DMT concentration from 0.05 to 0.01 v/w % significantly decreased all mechanical properties as well as significantly increased the sol fraction and swelling ratio. Also, increasing the crosslinking time at 37°C from 1 to 7 days significantly increased all mechanical properties and decreased both the sol fraction and swelling ratio. This study further showed that the flexural stiffness of ex vivo stabilized rabbit mandibles increased from 1.7 ± 0.3 N/mm with a traditional mini-plate fixator to 14.5 ± 4.1 N/mm for the 4:1 (0.05 v/w % DMT) PPF formulation at day 1. Overall, the formulations tested in this study were found to have properties suitable for potential further consideration in mandibular fracture fixation applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 529–538, 2015.

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2015

Journal Article

M. G. Sangeet Nair, Dr. Ullas Mony, Dr. Deepthy Menon, Dr. Manzoor K., Sidharthan, N., Pavithran, K., Shantikumar V Nair, and Krishnakumar N. Menon, “Development and molecular characterization of polymeric micro-nanofibrous scaffold of a defined 3-D niche for in vitro chemosensitivity analysis against acute myeloid leukemia cells”, International journal of nanomedicine, 2015.[Abstract]


Standard in vitro drug testing employs 2-D tissue culture plate systems to test anti-leukemic drugs against cell adhesion-mediated drug-resistant leukemic cells that harbor in 3-D bone marrow microenvironments. This drawback necessitates the fabrication of 3-D scaffolds that have cell adhesion-mediated drug-resistant properties similar to in vivo niches. We therefore aimed at exploiting the known property of polyurethane (PU)/poly-L-lactic acid (PLLA) in forming a micro-nanofibrous structure to fabricate unique, not presented before, as far as we are aware, 3-D micro-nanofibrous scaffold composites using a thermally induced phase separation technique. Among the different combinations of PU/PLLA composites generated, the unique PU/PLLA 60:40 composite displayed micro-nanofibrous morphology similar to decellularized bone marrow with increased protein and fibronectin adsorption. Culturing of acute myeloid leukemia (AML) KG1a cells in FN-coated PU/PLLA 60:40 shows increased cell adhesion and cell adhesion-mediated drug resistance to the drugs cytarabine and daunorubicin without changing the original CD34(+)/CD38(-)/CD33(-) phenotype for 168 hours compared to fibronectin tissue culture plate systems. Molecularly, as seen in vivo, increased chemoresistance is associated with the upregulation of anti-apoptotic Bcl2 and the cell cycle regulatory protein p27(Kip1) leading to cell growth arrest. Abrogation of Bcl2 activity by the Bcl2-specific inhibitor ABT 737 led to cell death in the presence of both cytarabine and daunorubicin, demonstrating that the cell adhesion-mediated drug resistance induced by Bcl2 and p27(Kip1) in the scaffold was similar to that seen in vivo. These results thus show the utility of a platform technology, wherein drug testing can be performed before administering to patients without the necessity for stromal cells.

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2015

Journal Article

S. BN, Dr. Ullas Mony, Dr. Deepthy Menon, VK, B., AG, M., and Shantikumar V Nair, “Bone Tissue Engineering with Multilayered Scaffolds-Part I: An Approach for Vascularizing Engineered Constructs In Vivo.”, Tissue Eng Part A., pp. 19-20, 2015.[Abstract]


Obtaining functional capillaries through the bulk has been identified as a major challenge in tissue engineering, particularly for critical-sized defects. In the present study, a multilayered scaffold system was developed for bone tissue regeneration, designed for through-the-thickness vascularization of the construct. The basic principle of this approach was to alternately layer mesenchymal stem cell-seeded nanofibers (osteogenic layer) with microfibers or porous ceramics (osteoconductive layer), with an intercalating angiogenic zone between the two and with each individual layer in the microscale dimension (100-400 μm). Such a design can create a scaffold system potentially capable of spatially distributed vascularization in the overall bulk tissue. In the cellular approach, the angiogenic zone consisted of collagen/fibronectin gel with endothelial cells and pericytes, while in the acellular approach, cells were omitted from the zone without altering the gel composition. The cells incorporated into the construct were analyzed for viability, distribution, and organization of cells on the layers and vessel development in vitro. Furthermore, the layered constructs were implanted in the subcutaneous space of nude mice and the processes of vascularization and bone tissue regeneration were followed by histological and energy-dispersive X-ray spectroscopy (EDS) analysis. The results indicated that the microenvironment in the angiogenic zone, microscale size of the layers, and the continuously channeled architecture at the interface were adequate for infiltrating host vessels through the bulk and vascularizing the construct. Through-the-thickness vascularization and mineralization were accomplished in the construct, suggesting that a suitably bioengineered layered construct may be a useful design for regeneration of large bone defects.

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2015

Journal Article

N. Vikkath, Valiyaveedan, S., Nampoothiri, S., Radhakrishnan, N., Pillai, G. S., Nair, V., Pooleri, G. Kumar, Mathew, G., Krishnakumar N. Menon, Ariyannur, P. S., and Pillai, A. B., “Genotype–phenotype analysis of von Hippel–Lindau syndrome in fifteen Indian families”, Familial Cancer, vol. 14, pp. 585–594, 2015.[Abstract]


The general prevalence of the familial multi-organ tumor disorder, von Hippel–Lindau syndrome (VHL), was estimated to be 1 in 25–40,000 in western studies two decades back. Few studies were done in Indian sub-continent, amidst a surge in clinical reports on VHL specific manifestations. The syndrome is correlated with mutations of the gene VHL (located in Chr 3p25.3). We aimed to conduct a prospective case series describing phenotypic and genotypic characteristics in Indian population. The VHL-specific clinical and radiological features were collected from patients and family members. Genotypic changes such as deletion/duplication or point mutation in the VHL locus were identified using sequencing and MLPA. Thirty-one subjects, from fifteen families with diagnosed VHL, were included in the study. Multicystic pancreas was found in 71 {%} (22/31), CNS hemangioblastoma in 68 {%} (21/31), renal cell carcinoma and retinal angiomas in 23 {%} (7/31) each, pheochromocytoma in 9.7 {%} (3/31) of the population and endolymphatic sac tumor in one subject. Four families (9 subjects) had full length deletion of VHL, three families (4 subjects) had a deletion of exon 3, eight families (18 subjects) had different exonic, splice-site and intronic point mutations and one subject had a de novo in-frame indel in exon 1. Multicystic pancreas and CNS hemangioblastomas were the most common manifestations in our population. The phenotypic expression patterns in terms of tumorigenesis, tissue tropism and penetrance in comparison to the genotypic features were found to be different from previous correlative studies.

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2015

Journal Article

N. Vadera, Anusha Ashokan, Gowd, G. S., Sajesh, K. M., Chauhan, R. P., Dr. Jayakumar Rangasamy, Shantikumar V Nair, and Dr. Manzoor K., “Manganese doped Nano-bioactive Glass for Magnetic Resonance Imaging”, Materials Letters, vol. 160, pp. 335 - 338, 2015.[Abstract]


Magnetic resonance imaging (MRI) is an attractive method to image biomaterial implants owing to its high spatial resolution and absence of ionizing radiation. However, most of the biomaterials lack magnetic contrast sufficient enough to be imaged in MRI. Here, we report synthesis of manganese doped nano-bioactive glass (Mn-nBG) giving bright contrast for MRI. We have optimized a room temperature method of doping nBG for efficient T1 weighted magnetic contrast. In vitro study using primary mesenchymal stem cells showed no toxicity for Mn-nBG up to a tested concentration of 100µg/ml, suggesting potential applications in cell labeling and tissue engineering.

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2015

Journal Article

Dr. Manzoor K., D, B., Girish C. M., A, S., and S, N., “Transferrin-Conjugated Biodegradable Graphene for Targeted Radiofrequency Ablation of Hepatocellular Carcinoma”, ACS Biomaterials Science and Engineering, vol. 1, no. 12, pp. 1211-9, 2015.[Abstract]


Radiofrequency ablation (RFA) is a clinically established therapy for hepatocellular carcinoma (HCC). However, because of poor radio-thermal conductivity of liver tissues, RFA is less efficient against relatively larger (>5 cm) liver tumors. Recently, nanoparticle-enabled RFA has emerged as a better strategy. On the basis of our recent understanding on biodegradability and novel electrothermal properties of graphene, herein, we report development of transferrin conjugated, biodegradable graphene (TfG) for RFA therapy. Cellular uptake studies using confocal microscopy and Raman imaging revealed significantly higher TfG uptake by HCC cells compared to bare graphene. TfG-treated cancer cells upon 5 min exposure to 100 W, 13.5 MHz RF showed >85% cell death, which was 4 times greater than bare graphene. Further evaluation in 3D (3 Dimensional) HCC culture system as well as in vivo rat models demonstrated uniform destruction of tumor cells throughout the 3D microenvironment. This study reveals the potential of molecularly targeted graphene for augmented RFA therapy of liver tumor.

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2015

Journal Article

A. Sasidharan, Swaroop, S., Koduri, C. K., Girish C. M., Chandran, P., Panchakarla, L. S., Somasundaram, V. H., Gowd, G. S., Shantikumar V Nair, and Dr. Manzoor K., “Comparative in Vivo Toxicity, Organ Biodistribution and Immune Response of Pristine, Carboxylated and PEGylated Few-layer Graphene Sheets in Swiss Albino Mice: A three month study”, Carbon, vol. 95, pp. 511 - 524, 2015.[Abstract]


We present a comprehensive 3 month report on the acute and chronic toxicity of intravenously administered (20&nbsp;mg&nbsp;kg−1) few-layer graphene (FLG) and, its carboxylated (FLG-COOH) and PEGylated (FLG-PEG) derivatives in Swiss albino mice. Whole-animal in&nbsp;vivo tracking studies revealed that irrespective of surface modifications, graphene predominantly accumulated in lungs over a period of 24&nbsp;h. Histological assessment and ex&nbsp;vivo confocal Raman spectral mapping revealed highest uptake and retention in lung tissue, followed by spleen, liver and kidney, with no accumulation in brain, heart or testis. FLG and FLG-COOH accumulated within organs induced significant cellular and structural damages to lungs, liver, spleen, and kidney, ranging from mild congestion to necrosis, fibrosis and glomerular filtration dysfunction, without appreciable clearance. Serum biochemistry analysis revealed that both FLG and FLG-COOH induced elevated levels of hepatic and renal injury markers. Quantitative RT-PCR studies conducted on 23 critical inflammation and immune response markers showed major alterations in gene expression profile by FLG, FLG-COOH and FLG-PEG treated animals. FLG-PEG in spite of its persistance within liver and spleen tissue for 3 months, did not induce any noticeable toxicity or organ damage, and displayed significant changes in Raman spectra, indicative of their biodegradation potential.

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2015

Journal Article

S. N. Rejinold, Baby, T., Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Multi Drug Loaded Thermo-Responsive Fibrinogen-graft-Poly(N-vinyl Caprolactam) Nanogels for Breast Cancer Drug Delivery”, Journal of Biomedical Nanotechnology, vol. 11, pp. 392-402, 2015.[Abstract]


This study aims at the targeted delivery of 5-fluorouracil (5-FU) and Megestrol acetate (Meg) loaded fibrinogen-graft-poly(N-Vinyl caprolactam) nanogels (5-FU/Meg-fib-graft-PNVCL NGs) toward 5 1-integrins receptors expressed on breast cancer cells to have enhanced anti-cancer effect in vitro. To achieve this aim, we developed biocompatible thermoresponsive fib-graft-PNVCL NGs using fibrinogen and carboxyl terminated PNVCL via EDC/NHS amidation reaction. The Lower Critical Solution Temperature (LCST) of fib-graft-PNVCL could be tuned according to PNVCL/fibrinogen compositions. The 100120 nm sized nanogels of fib-graft-PNVCL (LCST = 35 \textpm 1 \textdegreeC) was prepared using CaCl2 cross-linker. The 5-FU/Meg-fib-graft-PNVCL NGs showed a particle size of 150170 nm size. The drug loading efficiency with 5-FU was 62% while Meg showed 74%. The 5-FU and Meg release was prominent above LCST than below LCST. The multi drug loaded fib-graft-PNVCL NGs showed enhanced toxicity, apoptosis and uptake by breast cancer (MCF-7) cells compared to their individual doses above their LCST. The in vivo assessment in Swiss albino mice showed sustained release of Meg and 5-FU as early as 3 days, confirming the therapeutic efficiency of the formulation. These results demonstrate an enhanced platform for the future animal studies on breast tumor xenograft model.

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2015

Journal Article

K. T. Shalumon, Deepthi, S., Anupama, M. S., Nair, S. V., Dr. Jayakumar Rangasamy, and Chennazhi, K. P., “Fabrication of Poly (l-lactic acid)/gelatin Composite Tubular Scaffolds for Vascular Tissue Engineering”, International Journal of Biological Macromolecules, vol. 72, pp. 1048 - 1055, 2015.[Abstract]


The in vitro fabrication of fully functional 3D vascular tissue construct represents one of the most fundamental challenges in vascular tissue engineering. Polymer blending is an effective method for developing, desirable bio-composites for tissue engineering. This study employs the blending of desired characteristics of a synthetic polymer, poly (l-lactic acid) (PLLA) and a biopolymer, gelatin for enhancing cell adhesion sites. Aligned and random PLLA/gelatin nanofibers were fabricated using electrospinning technique. Morphological and chemical characterization of the nanofibrous scaffolds was carried out and the size of fibers ranged from 100 to 500nm. The SEM, fluorescent staining and viability assays revealed an increase in viability and proliferation of Human Umbilical Vein Endothelial Cells (HUVECs) and Smooth Muscle Cells (SMCs) proportional to gelatin content. The aligned fiber morphology helps cells to orient and elongate along their long axis. Thus the results were suggestive of the fact that topographically aligned nanofibrous scaffolds control cellular organization and possibly provide a good support for achieving the vital organization and physical properties of blood vessel.

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2015

Journal Article

S. N. Rejinold, Thomas, R. George, Muthiah, M., Chennazhi, K. P., Manzoor, K., Park, I. - K., Jeong, Y. Yeon, and Dr. Jayakumar Rangasamy, “Anti-cancer, Pharmacokinetics and Tumor Localization Studies of pH-, RF- and Thermo-Responsive Nanoparticles”, International Journal of Biological Macromolecules, vol. 74, pp. 249 - 262, 2015.[Abstract]


The curcumin-encapsulated chitosan-graft-poly(N-vinyl caprolactam) nanoparticles containing gold nanoparticles (Au-CRC-TRC-NPs) were developed by ionic cross-linking method. After “optimum RF exposure” at 40W for 5min, Au-CRC-TRC-NPs dissipated heat energy in the range of ∼42°C, the lower critical solution temperature (LCST) of chitosan-graft-poly(N-vinyl caprolactam), causing controlled curcumin release and apoptosis to cancer cells. Further, in vivo PK/PD studies on swiss albino mice revealed that Au-CRC-TRC-NPs could be sustained in circulation for a week with no harm to internal organs. The colon tumor localization studies revealed that Au-CRC-TRC-NPs were retained in tumor for a week. These results throw light on their feasibility as multi-responsive nanomedicine for RF-assisted cancer treatment modalities

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2015

Journal Article

A. R. Kumar, Sivashanmugam, A., Deepthi, S., Iseki, S., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Injectable Chitin-Poly(ε-caprolactone)/Nanohydroxyapatite Composite Microgels Prepared by Simple Regeneration Technique for Bone Tissue Engineering”, ACS Applied Materials & Interfaces, vol. 7, pp. 9399-9409, 2015.[Abstract]


Injectable gel systems, for the purpose of bone defect reconstruction, have many advantages, such as controlled flowability, adaptability to the defect site, and increased handling properties when compared to the conventionally used autologous graft, scaffolds, hydroxyapatite blocks, etc. In this work, nanohydroxyapatite (nHAp) incorporated chitin-poly(ε-caprolactone) (PCL) based injectable composite microgels has been developed by a simple regeneration technique for bone defect repair. The prepared microgel systems were characterized using scanning electron microscope (SEM), Fourier transformed infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The composite microgel, with the incorporation of nHAp, showed an increased elastic modulus and thermal stability and had shear-thinning behavior proving the injectability of the system. The protein adsorption, cytocompatibility, and migration of rabbit adipose derived mesenchymal stem cells (rASCs) were also studied. Chitin-PCL-nHAp microgel elicited an early osteogenic differentiation compared to control gel. The immunofluorescence studies confirmed the elevated expression of osteogenic-specific markers such as alkaline phosphatase, osteopontin, and osteocalcin in chitin-PCL-nHAp microgels. Thus, chitin-PCL-nHAp microgel could be a promising injectable system for regeneration of bone defects which are, even in deeper planes, irregularly shaped and complex in nature.

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2015

Journal Article

M. Vishnu Priya, Kumar, R. Arun, Sivashanmugam, A., Nair, S. Vasudevan, and Dr. Jayakumar Rangasamy, “Injectable Amorphous Chitin-Agarose Composite Hydrogels for Biomedical Applications”, Journal of Functional Biomaterials, vol. 6, pp. 849–862, 2015.[Abstract]


Injectable hydrogels are gaining popularity as tissue engineering constructs because of their ease of handling and minimal invasive delivery. Making hydrogels from natural polymers helps to overcome biocompatibility issues. Here, we have developed an Amorphous Chitin (ACh)-Agarose (Agr) composite hydrogel using a simpletechnique. Rheological studies, such as viscoelastic behavior (elastic modulus, viscous modulus, yield stress, and consistency), inversion test, and injectability test, were carried out for different ACh-Agr concentrations. The composite gel, having a concentration of 1.5% ACh and 0.25% Agr, showed good elastic modulus (17.3 kPa), yield stress (3.8 kPa), no flow under gravity, injectability, and temperature stability within the physiological range. Based on these studies, the optimum concentration for injectability was found to be 1.5% ACh and 0.25% Agr. This optimized concentration was used for further studies and characterized using FT-IR and SEM. FT-IR studies confirmed the presence of ACh and Agr in the composite gel. SEM results showed that the lyophilized composite gel had good porosity and mesh like networks. The cytocompatibility of the composite gel was studied using human mesenchymal stem cells (hMSCs). The composite gels showed good cell viability.These results indicated that this injectable composite gel can be used for biomedical applications.

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2015

Journal Article

J. Venkatesan, Dr. Jayakumar Rangasamy, Anil, S., Chalisserry, E. P., Pallela, R., and Kim, S. - K., “Development of Alginate-Chitosan-Collagen Based Hydrogels for Tissue Engineering”, Journal of Biomaterials and Tissue Engineering, vol. 5, pp. 458-464, 2015.[Abstract]


In the recent times, significant development has been achieved in the tissue engineering field using alginate and chitosan. Moreover, hydrogels of these successful macromolecules contribute enormously towards the development of novel biomedical materials. The present paper depicts the preparation and analysis of different kinds of hydrogels using the combination of alginate, chitosan, chitooligosacchrides and collagen (alginate-chitosan-cos-collagen), and also tested in vitro with human keratinocyte (HaCaT) cells for considering these composites as skin tissue substitute. Furthermore, the prepared hydrogels are chemically characterized, where the total porosity of the scaffold is found to be &gt;90% with 33500 m of pore size. The newly developed scaffolds through freeze-drying method showed excellent biocompatibility, cell adhesion and proliferation with HaCaT cells. Addition of collagen, alginate with chitosan hydrogel further improved the biocompatible nature that mimics the functional environment of skin.

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2015

Journal Article

Dr. Jayakumar Rangasamy, M, A., T., S. Kumar. P., Raja Biswas, and K, L. V., “Exploration of Alginate Hydrogel/Nano Zinc Oxide Composite Bandages for Infected Wounds”, International Journal of Nanomedicine, vol. 10, pp. 53-66, 2015.

2015

Journal Article

Dr. Jayakumar Rangasamy, S, S., P, C. K., H, A., and P, J., “Periodontal Specific Differentiation of Dental Follicle Stem Cells into Osteoblast, Fibroblast and Cementoblast”, Tissue Engineering-C: Methods, vol. 21, no. 10, pp. 1044-1058, 2015.

2015

Journal Article

A. Sasidharan, Sivaram, A. J., Retnakumari, A. P., Chandran, P., Malarvizhi, G. Loghanatha, Nair, S., and Dr. Manzoor K., “Radiofrequency Ablation of Drug-Resistant Cancer Cells Using Molecularly Targeted Carboxyl-Functionalized Biodegradable Graphene”, Advanced Healthcare Materials, vol. 4, pp. 679-684, 2015.[Abstract]


Under ultralow radiofrequency (RF) power, transferrin-conjugated graphene nanoparticles can thermally ablate drug- or radiation-resistant cancer cells very effectively. The results suggest that graphene-based RF hyperthermia can be an efficient method to manage drug-/radiation-resistant cancers.

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2015

Journal Article

M. W. Calik, Dr. Sahadev Shankarappa, Langert, K. A., and Stubbs, Jr, E. B., “Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress”, ASN Neuro, vol. 7, p. 1759091415595726, 2015.[Abstract]


A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain–Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.2 km/day × 3 weeks) prior to P2-antigen induction of EAN. Sedentary rats developed a monophasic course of EAN beginning on postimmunization day 12.3 ± 0.2 and reaching peak severity on day 17.0 ± 0.3 (N = 12). By comparison, forced-exercise preconditioned rats exhibited a similar monophasic course but with significant (p &lt; .05) reduction of disease severity. Analysis of popliteal lymph nodes revealed a protective effect of exercise preconditioning on leukocyte composition and egress. Compared with sedentary controls, forced exercise preconditioning promoted a sustained twofold retention of P2-antigen responsive leukocytes. The percentage distribution of pro-inflammatory (Th1) lymphocytes retained in the nodes from sedentary EAN rats (5.1 ± 0.9%) was significantly greater than that present in nodes from forced-exercise preconditioned EAN rats (2.9 ± 0.6%) or from adjuvant controls (2.0 ± 0.3%). In contrast, the percentage of anti-inflammatory (Th2) lymphocytes (7–10%) and that of cytotoxic T lymphocytes (∼20%) remained unaltered by forced exercise preconditioning. These data do not support an exercise-inducible shift in Th1:Th2 cell bias. Rather, preconditioning with forced exercise elicits a sustained attenuation of EAN severity, in part, by altering the composition and egress of autoreactive proinflammatory (Th1) lymphocytes from draining lymph nodes.

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2015

Journal Article

P. Chandran, Pavithran, K., Sidharthan, N., Sasidharan, A., Nair, S., and Koyakutty, M., “Protein Nanomedicine Exerts Cytotoxicity toward CD34+ CD38– CD123+ Leukemic Stem Cells”, ACS Biomaterials Science & Engineering, vol. 1, pp. 1194-1199, 2015.[Abstract]


The efficacy of protein-vorinostat nanomedicine (NV) is demonstrated in leukemic stem cells (LSC) isolated from refractory acute myeloid leukemia (AML) patient samples, where it successfully ablated both CD34+ CD38– CD123+ LSC and non-LSC “leukemic blast” compartments, without inducing myelosuppression or hemotoxicity. Besides, NV also exerted excellent synergistic lethality against leukemic bone marrow cells (BMC) at lower concentrations (0.1 μM) in combination with DNA methyltransferase (DNMT) inhibitor, decitabine. Considering the extermination of resilient LSC and synergism with decitabine, NV shows promise for clinical translation in the setting of a more tolerable and effective epigenetic targeted therapy for leukemia

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2015

Journal Article

N. H.A., K.S., S., R.C., K., Shantikumar V Nair, and K., L. V., “Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells”, Current Drug Delivery, 2015.[Abstract]


Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

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2015

Journal Article

M. P. Antony, Moehl, T., Wielopolski, M., Moser, J. - E., Nair, S., Yu, Y. - J., Kim, J. - H., Kay, K. - Y., Jung, Y. - S., Yoon, K. Byung, Grätzel, C., Zakeeruddin, S. M., and Gratzel, M., “Long-Range π-Conjugation in Phenothiazine-containing Donor–Acceptor Dyes for Application in Dye-Sensitized Solar Cells”, ChemSusChem, vol. 8, pp. 3859-3868, 2015.[Abstract]


<p>Abstract Four organic donor–π-bridge–acceptor dyes containing phenothiazine as a spacer and cyanoacrylic acid as an acceptor were synthesized and tested as sensitizers in dye-sensitized solar cells (DSCs). The influence of iodide- and cobalt-based redox electrolytes on the photovoltaic device performance was investigated. In these new dyes, systematic π-conjugation was extended by inserting one or two phenothiazine moieties and investigated within the context of the resulting photoinduced charge-transfer properties. A detailed investigation, including transient absorption spectroscopy and quantum chemical methods, provided important information on the role of extended π-conjugation on the photophysical properties and photovoltaic device performance. Overall, the results showed that the extension of π-conjugation by one phenothiazine unit resulted in the best device performance owing to reduced recombination rates, whereas extension by two phenothiazine units reduced dye adsorption on TiO2 probably owing to the increase in molecular size. The performance of the dyes in DSCs was found to be a complex interaction between dye structure and size.</p>

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2015

Journal Article

G. G., A.M., A., SIVAKUMAR N, A., B., S.V., N., and K.R.V., S., “Photocatalytic Applications of Electrospun TiO2 Nanofibres Embedded with Bimodal Sized and Prismatic Gold Nanoparticles”, Journal of Nanoscience and Nanotechnology, 2015.[Abstract]


In this paper, we have synthesized electrospun TiO2 nanofibers embedded with bimodal sized and prismatic gold nanoparticles. The surface plasmons generated in the gold nanoparticles were used to enhance the performance of photocatalysis. The photocatalytic conversion efficiencies of these bimodal sized/prismatic gold nanoparticles when embedded in electrospun TiO2 fibres showed an enhancement of upto 60% over bare fiber systems and also show higher efficiencies than electrospun fibrous systems embedded with unimodal sized gold nanoparticles. Anisotropic bimodal gold nanoparticles show the highest degree of photocatalytic activity. This may be attributed to greater density/concentration of nanoparticles with higher effective surface area and formation of a junction between the smaller and larger nanoparticles. Such a bimodally distributed range of nanoparticles could also lead to greater trapping of charge carriers at the TiO2 conduction band edge and promoting catalytic reactions on account of these trapped charges. This enhanced photocatalytic activity is explained by invoking different operating mechanisms such as improved surface area, greater trapping, coarse plasmon resonance and band effects. Thus, a useful applicability of the gold nanoparticles is shown in the area of photocatalysis.

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2015

Journal Article

R. A.K. and J., K., “High Reversible Capacity and Rate Capability of ZnCo2O4 Graphene Nanocomposite Anode for High Performance Lithium Ion Batteries”, Solid State Sciences, 2015.

2015

Journal Article

M. C.C, A.M., C., A, P., ,, S.V., N., K, C., and D., M., “Nanotextured Stainless Steel for Improved Corrosion Resistance and Biological Response in Coronary Stenting”, Nanoscale, no. 2, 2015.[Abstract]


Nanosurface engineering of metallic substrates for improved cellular response is a persistent theme in biomaterials research. The need to improve the long term prognosis of commercially available stents has led us to adopt a ‘polymer-free’ approach which is cost effective and industrially scalable. In this study, 316L stainless steel substrates were surface modified by hydrothermal treatment in alkaline pH, with and without the addition of a chromium precursor, to generate a well adherent uniform nanotopography. The modified surfaces showed improved hemocompatibility and augmented endothelialization, while hindering the proliferation of smooth muscle cells. Moreover, they also exhibited superior material properties like corrosion resistance, surface integrity and reduced metal ion leaching. The combination of improved corrosion resistance and selective vascular cell viability provided by nanomodification can be successfully utilized to offer a cell-friendly solution to the inherent limitations pertinent to bare metallic stents.

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2015

Journal Article

, P., P., K.V., S., A., B., K.R.V., S., V.S., N., Y.S., L., and N., S., “Electrochemical performance of electrophoretically deposited nanostructured LiMnPO4-sucrose derived carbon composite electrodes for lithium ion batteries”, Journal of Nanoscience and Nanotechnology, 2015.[Abstract]


The present study reports an approach by which thin films of sucrose added olivine type LiMnPO4-C composite and pristine LiMnPO4 is made by a technique of electrophoretic co-deposition in which pristine and composite samples were synthesized by a sol–gel route. These thin films with enhanced surface area is used to fabricate cathodes for rechargeable Li ion batteries. XRD confirms phase pure single crystalline orthorhombic structure. Transmission Electron Microscopy (TEM) images shows the carbon coating over LiMnPO4 and the particle size restricted in the nano regime. The presence of sp2 hybridized carbon on LiMnPO4 particles is confirmed by X-ray Photon spectroscopy (XPS). To explore the electrochemical behavior, cyclic voltammetry (CV) and cycling studies were performed. The specific capacity for LiMnPO4-C is found to be increased by 43% in comparison to the pristine LiMnPO4. It also exhibited 86% retention in capacity compared to the pristine LiMnPO (52%). The result indicates that a proper carbon coating can significantly improve the electronic conductivity and hence the specific capacity.

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2015

Journal Article

S. M.S., G., B., P., P., K.R.V., S., Y.S., L., V., S. Nair, and N., S., “Electrochemical Performance of PbO2and PbO2-CNT Composite Electrodes for Energy Storage Devices”, Journal of Nanoscience and Nanotechnology, 2015.[Abstract]


In this work we report the electrochemical performance comparison of two new hybrid supercapacitors one based on graphene as negative electrode and lead dioxide thin film as positive electrode and the other with graphene as negative electrode and lead dioxide-carbon nanotube composite as positive electrode in 0.1 M KOH electrolyte. In the present work, PbO2 was synthesized using sol–gel method which is one of the promising materials for hybrid supercapacitors. The XRD confirmed the single phase of the PbO2 and the grain size is 39 nm which has been determined using Scherrer's formula. Thin films of PbO2, PbO2–CNT composite and graphene were coated on the titanium substrate by electrophoretic deposition. Further material characterisation has been carried out using SEM, TEM, XPS and electrochemical characterisation using CV, charge/discharge and electrochemical impedance spectroscopy (EIS) for obtaining energy density and power density, cyclic stability and internal resistance respectively. The present results revealed that PbO2–CNT composite/graphene asymmetric hybrid supercapacitor exhibits large specific capacitance and energy density over PbO2/graphene based system. The PbO2–CNT composite/graphene asymmetric hybrid supercapacitor exhibited maximum power density and energy density of 1200 W/Kg and 65 Wh/Kg respectively at a current density of 2 A/g. The PbO2–CNT composite/graphene asymmetric hybrid system exhibited excellent cycling stability with the capacitance retained 85% of its maximum value up to 3000 cycles.

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2015

Journal Article

A. Nikhil, Anjusree, G. S., Nair, S. V., and A. Nair, S., “Visible light-induced photocatalytic activity of high surface area N-doped two-dimensional (2-D) TiO2 sheets”, RSC Adv., vol. 5, pp. 88464-88470, 2015.[Abstract]


TiO2 being a wide band-gap material offers photocatalytic activity only in the UV region. The effects of simultaneously improving the surface area and nitrogen doping on the visible light-assisted photocatalytic activity of titanate-derived two-dimensional (2-D) sheets of TiO2 have been investigated. Results indicate a remarkable efficiency in the photocatalytic degradation of methyl orange in an aqueous environment when compared to undoped 2-D TiO2 sheets.

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2015

Journal Article

B. S.N., H.C., L., M.C, C., J.K., R., A., B., and T.N., K., “Facile Synthesis of Hydroxyapatite by Hydrothermal and Solvent Combustion Methods”, Korean Journal of Materials Research, 2015.

2015

Journal Article

S. K.S, R.S, N., V., N. S., R., K. C., and K., L. V., “Combination of Anti-diabetic Drug Metformin and Boswellic acid Nanoparticles: A Novel Strategy for Pancreatic Cancer Therapy”, Journal of Biomedical Nanotechnology, 2015.[Abstract]


Pancreatic cancer has an infaust prognosis and is the fourth common cause of cancer related death in India. It is highly resistant to conventional treatment modalities such as chemotherapy, radiation therapy and surgery. The association of pancreatic cancer and diabetes mellitus is explored in our study. Pancreatic cancer is more likely to occur in people who have diabetes than people devoid of it, which is supported by the observation that hyperglycaemia occurs at an early stage of pancreatic cancer and is indeed a risk factor. In the present study, we have demonstrated a synergistic relationship between metformin and boswellic acid nanoparticles with varying doses of boswellic acid nanoparticles and constant metformin (20 mM). The effect revealed increased synergism between metformin and boswellic acid nanoparticles through the inhibition of cell proliferation with an effect of 80% for the combination with 0.3 mg/mL and 0.4 mg/mL and a constant concentration of metformin. We examined the effect of combination on cell migration which revealed time dependent inhibitory effect on pancreatic cell line (MiaPaCa-2). Also, we found that the combinatorial approach significantly decreased colony formation and exhibited high rate of induction of apoptosis through DNA fragmentation in pancreatic cancer cells. In-vitro hemolysis confirmed the hemocompatibility of the combination therapy with metformin and boswellic acid nanoparticles. Flow cytometry based apoptosis assay and Caspase mediated apoptosis proved apoptosis mediated cell death. Further, the cells were analysed with mitochondrial membrane potential kit which revealed depolarization of mitochondrial membrane potential due to apoptosis after treatment with drug combination. Hence, the combination approach proved to be a promising therapy towards pancreatic cancer.

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2015

Journal Article

R. N., ,, and H.K., V., “Hybrid fields unleashing wider scope in research frontiers: Editorial”, Trends in Biomaterials and Artificial Organs, 2015.

2015

Journal Article

B. S., J.-K., R., M.C., C., A., B., and T.N., K., “Synthesis of Calcium Phosphate Minerals from Biowaste Clam Shells using Microwave Heating”, Korean Journal of Materials Research, 2015.

2015

Journal Article

P. P., K., S., A.M., A., Manjusha Nair, S.V., N., R., B., T.N., K., and A., B., “Role of Nanogrooves on the Performance of Ultra-fine Grained Titanium as a Bio-Implant”, Advanced Nanomaterials: Synthesis, Properties, and Applications, 2015.

2014

Journal Article

Pa Anjali, Sonia, T. Sa, Shakir, Ib, Nair, S. Va, and Balakrishnan, Aa, “On the synthesis and electrochemical characterization of ordered hierarchical NiO micro bouquets with trimodal pore size distribution”, Journal of Alloys and Compounds, vol. 618, pp. 396-402, 2014.[Abstract]


The present study demonstrates a novel approach by which 'bulk nanostructured' NiO micro bouquets can be processed into a high surface area electrode for supercapacitor applications. A detailed study has been performed to elucidate the impact of porosity and redox reactions on the electrochemical behavior. The spheres were synthesized using a soft template technique. An intrinsic correlation between the surface area, capacitance and the internal resistance has been deduced and explained on the basis of relative contributions from the faradic properties of NiO. These NiO spheres exhibited specific mass capacitance values as high as 1950 F g-1. Further, coin cells employing these rechargeable electrodes were also demonstrated which exhibits energy and power densities of 17 W h kg-1and 24 kW kg-1. It has been shown that these electrodes based on such bulk nanostructures can allow significant room for high performance supercapacitor devices.

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2014

Journal Article

D. Narayanan, Dr. Jayakumar Rangasamy, and Chennazhi, K. P., “Versatile carboxymethyl chitin and chitosan nanomaterials: A review”, Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, vol. 6, pp. 574-598, 2014.[Abstract]


<p>Biocompatibility, biodegradability, and low cost of chitin and chitosan have drawn immense attention in many fields including medicine, bioinspired material science, pharmaceuticals, and agriculture. Their handling and processing are difficult owing to its insolubility in neutral aqueous solution or organic solvents. One of the methods used to improve the solubility characteristics of chitin and chitosan is chemical modification. Introducing a carboxymethyl group is the most advantageous method of increasing the solubility of chitosan at neutral and alkaline pH. Carboxymethyl chitin (CMC) and carboxymethyl chitosan (CMCS) are water soluble derivatives formed by introducing CH2COOH function into the polymer which endows it with better biological properties. The functional group makes CMC/CMCS nanoparticles (NPs) efficient vehicles for the delivery of DNA, proteins, and drugs. This review provides an overview of the characteristics of CMC/CMCS NPs as well as fulfills the task of describing and discussing its important roles primarily in cancer nanomedicine detailing the targeted drug delivery aspect. The application of these NPs in imaging, agriculture, and textiles has also been highlighted. The review also elaborates the advantages of using the CMC and CMCS NPs for drug and gene delivery.</p>

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2014

Journal Article

A. Paravannoor, S. Sebastian, T., Nair, S. K. V., and Balakrishnan, A., “Synthesis and characterization of mesoporous NiO nano-hexagons with 110 exposed facets on worm like nickel backbone”, Materials Letters, vol. 135, pp. 180-183, 2014.[Abstract]


The present study reports the synthesis of NiO hexagons with exposed {110} facets on metallic Ni backbones. Intrinsic correlations were deduced between the surface area, crystalline anisotropy and the electrochemical performance. These metal backboned hexagons were employed as supercapacitor electrodes exhibiting specific mass capacitance value as high as 2100 Fg-1. Further, a working model button cell employing these rechargeable electrodes is also demonstrated exhibiting an energy and power density of 17 Wh kg-1and 3.5 kW kg-1, respectively. © 2014 Elsevier B.V.

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2014

Journal Article

Sac Bramhe, Kim, T. Na, Balakrishnan, Ab, and Chu, M. Ccd, “Conversion from biowaste Venerupis clam shells to hydroxyapatite nanowires”, Materials Letters, vol. 135, pp. 195-198, 2014.[Abstract]


The present study demonstrates a novel approach by which biowaste clam shells derived from Venerupis species can be processed into high aspect ratio one dimensional wires being an interesting candidate to biomedical applications. These nanowires were synthesized hydrothermally and exhibited an aspect ratio in the order of 102 with a surface area of 40 m2 g -1 and narrowly distributed diameter size range from 40 to 130 nm. Fast Fourier transform analysis during high resolution transmission electron microscopy showed the wires exhibiting growth along (300). X-ray diffractometry and Fourier-transform Infra-red spectroscopy showed that the nanowires produced were of high purity. © 2014 Elsevier B.V.

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2014

Journal Article

, “A review on 'self-cleaning and multifunctional materials'”, Journal of Materials Chemistry A, vol. 2, pp. 14773-14797, 2014.[Abstract]


This review article exemplifies the importance of self-cleaning materials and coatings. Self-cleaning coatings are becoming an integral part of our daily life because of their utility in various applications such as windows, solar panels, cements, and paints. In this review, various categories of materials for the fabrication of hydrophilic, hydrophobic, oleophobic, amphiphobic and multifunctional coatings and their synthesis routes have been discussed. Furthermore, different natural organisms exhibiting superhydrophobic behaviour have been analysed. This review also covers the fundamentals of self-cleaning attributes such as water contact angle, surface energy, and contact angle hysteresis. © the Partner Organisations 2014.

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2014

Journal Article

V. Lakshmi, Ranjusha, R., Vineeth, S., Balakrishnan, A., and Shantikumar V Nair, “Supercapacitors based on microporous β-Ni(OH)2 nanorods”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 457, pp. 462-468, 2014.[Abstract]


A peculiar architecture of a novel class one dimensional β-Ni(OH)2 nanorods synthesized by an optimized surfactant-free aqueous precipitation route has been lucratively exploited to fabricate highly efficient microporous electrodes for supercapacitors. These fabricated electrodes comprised of a highly porous overlay of interconnected nanoscale units with rod-shaped profile which terminates into jagged-like morphology. The surface area of these nanorods was found to be  91m2g-1. This architecture transcribes into a superior cycling performance (capacitance of 1150Fg-1 was achieved) with more than 99% of the initial capacitance being retained after 5000 charging/discharging cycles. Their outstanding intercalation/de-intercalation prerogatives have also been exploited to fabricate supercapacitor coin cells which reveal a significant power density of 52kWkg-1 and energy density of 4Whkg-1 with extremely fast response time of 1.2ms. © 2014 Elsevier B.V.

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2014

Journal Article

La Li, Zhu, Pb, Peng, Sa, Srinivasan, Ma, Yan, Qa, Nair, A. Sc, Liu, Bd, and Samakrishna, Sb, “Controlled growth of CuS on electrospun carbon nanofibers as an efficient counter electrode for quantum dot-sensitized solar cells”, Journal of Physical Chemistry C, vol. 118, pp. 16526-16535, 2014.[Abstract]


One-dimensional CuS/electrospun carbon nanofiber heteroarchitectures (CuS/EC) with high catalytic activity have been successfully fabricated by combining the versatility of the electrospinning technique and following a hydrothermal process. The CuS nanoparticles as the secondary nanostructures were uniformly grown on the primary electrospun carbon nanofibers with good dispersion by optimizing reaction conditions. It was found that the l-cysteine used as the sulfur donor and chelating reagent was favored for the growth of CuS on the carbon fibers. A possible formation mechanism and growth process of the CuS nanoparticles on the carbon fibers is discussed based on the experimental results. The as-prepared CuS/EC composite was then spray-deposited on FTO glass and demonstrated good performance in quantum dot-sensitized solar cells (QDSCs), which was higher than the conventional Pt electrode. The good performance is attributed to its heteroarchitecture. The CuS nanoparticles with high catalytic activity play the main role in the reduction process of the oxidized polysulfide, while the carbon nanofibers with the 3-D mat morphology bridge all the CuS nanoparticles as the framework and facilitate the charge transport during the catalysis process. © 2014 American Chemical Society.

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2014

Journal Article

G. L. Malarvizhi, Retnakumari, A. P., Nair, S., and Dr. Manzoor K., “Transferrin Targeted Core-shell Nanomedicine for Combinatorial Delivery of Doxorubicin and Sorafenib Against Hepatocellular Carcinoma”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 10, pp. 1649-1659, 2014.[Abstract]


Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing >. 75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in  . 92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. From the Clinical Editor: Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. © 2014 Elsevier Inc.

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2014

Journal Article

S. Fazal, Jayasree, A., Sasidharan, S., Menon, D., Koyakutty, M., and Shantikumar V Nair, “Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer”, ACS Applied Materials and Interfaces, vol. 6, pp. 8080-8089, 2014.[Abstract]


Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm2 proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy. © 2014 American Chemical Society.

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2014

Journal Article

D. Sankar, Shalumon, K. T., Chennazhi, K. P., Menon, D., and Dr. Jayakumar Rangasamy, “Surface plasma treatment of poly(caprolactone) micro, nano, and multiscale fibrous scaffolds for enhanced osteoconductivity”, Tissue Engineering - Part A, vol. 20, pp. 1689-1702, 2014.[Abstract]


In this study, poly(caprolactone) (PCL) was electrospun to nano, micro, and multiscale (micro-nano) fibers, which were then subjected to low pressure argon and nitrogen plasma treatment. The electrospun fibers contain microfibers of diameter 8-10?μm and nanofibers of diameter 200-300?nm. Characterization of the plasma-treated fibers showed that treatment using less oxidizing gas like nitrogen and inert gas like argon functionalize the surface with polar groups that significantly modify the properties of the scaffold. Highly hydrophobic PCL fibrous scaffolds were rendered hydrophilic, with significantly improved biomineralization after the plasma treatment. While plasma treatment on micro and multiscale fibers enhanced their protein adsorption, cell attachment, spreading, elongation, and proliferation, nanofibers showed remarkably improved cell attachment. The applicability of plasma-treated electrospun fibers for differentiation of mesenchymal stem cell toward osteogenic lineage was also studied. Accelerated differentiation toward osteoblast lineage, with maximum alkaline phosphatase (ALP) activity in 14 days was achieved in plasma-treated fibers. Another remarkable outcome was the enhanced ALP activity of the microfibers after plasma treatment, compared with multiscale and nanofibers. Alizarin red staining further confirmed the mineralization of the plasma-treated scaffolds, indicative of maturation of the differentiated cells. This work thus concentrates on harnessing the potential of plasma treatment, for improving the osteoconductivity of fibrous scaffolds, which could be used for bone tissue engineering/regenerative medicine. © Copyright 2014, Mary Ann Liebert, Inc. 2014.

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2014

Journal Article

A. Anitha, Sreeranganathan, M., Chennazhi, K. P., Lakshmanan, V. - K., and Dr. Jayakumar Rangasamy, “In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies”, European Journal of Pharmaceutics and Biopharmaceutics, 2014.[Abstract]


Colon cancer is the third most leading causes of death due to cancer worldwide and the chemo drug 5-fluorouracil's (5-FU) applicability is limited due to its non-specificity, low bioavailability and overdose. The efficacy of 5-FU in colon cancer chemo treatment could be improved by nanoencapsulation and combinatorial approach. In the present study curcumin (CUR), a known anticancer phytochemical, was used in combination with 5-FU and the work focuses on the development of a combinatorial nanomedicine based on 5-FU and CUR in N,O-carboxymethyl chitosan nanoparticles (N,O-CMC NPs). The developed 5-FU-N,O-CMC NPs and CUR-N,O-CMC NPs were found to be blood compatible. The in vitro drug release profile in pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days. The combined exposure of the nanoformulations in colon cancer cells (HT 29) proved the enhanced anticancer effects. In addition, the in vivo pharmacokinetic data in mouse model revealed the improved plasma concentrations of 5-FU and CUR which prolonged up to 72 h unlike the bare drugs. In conclusion, the 5-FU and CUR released from the N,O-CMC NPs produced enhanced anticancer effects in vitro and improved plasma concentrations under in vivo conditions. © 2014 Elsevier B.V. All rights reserved.

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2014

Journal Article

M. Vab Reddy, Jie, T. Wac, Jafta, C. Jd, Ozoemena, K. Ide, Mathe, M. Kd, Nair, A. Sf, Peng, S. Sg, Idris, M. Sg, Balakrishna, Gh, Ezema, F. Ii, and Chowdari, B. V. Ra, “Studies on Bare and Mg-doped LiCoO2 as a cathode material for Lithium ion Batteries”, Electrochimica Acta, vol. 128, pp. 192-197, 2014.[Abstract]


In this paper, we report on the preparation of bare and Mg-doped Li(Mg xCo1-x)O2 (x = 0, 0.03, 0.05) phases by a molten salt method and their electrochemical properties. They were prepared at 800 °C for 6 h in air. Rietveld refined X-Ray Diffraction data of bare (x = 0) and Mg-doped (x = 0.03, 0.05) compounds show a well-ordered hexagonal layer-type structure (a ∼ 2.81 Å, c ∼ 14.05 Å). Scanning Electron Microscopy (SEM) show hexagonal type morphology at 800°C. Powder density was close to 5.02 gcm-3, which compares well with the theoretical value. Electrochemical properties were studied in the voltage range of 2.5-4.3 V vs. Li using Cyclic Voltammetry (CV) and galvanostatic cycling. CV studies on bare and Mg-doped LiCoO2 show main cathodic and anodic redox peaks at ∼ 3.9 V and ∼ 4.0 V, respectively. Galvanostatic cycling of Li(MgxCo1-x)O2 (x = 0, 0.03, 0.05) showed reversible capacity values at the 60th cycle to be: 147 (±3) mAh g-1 (x = 0), 127 (±3) mAh g-1 (x = 0.03), and 131 (±3) mAh g-1 (x = 0.05) cycled at a current density of 30 mA g-1. Capacity retention is also favourable at 98.5%. © 2013 Published by Elsevier Ltd. All rights reserved.

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2014

Journal Article

S. Roshny, Ranjusha, R., Deepak, M. S., N. Rejinold, S., Dr. Jayakumar Rangasamy, Nair, S. V., and Balakrishnan, A., “MnO2 nano/micro Hybrids for Supercapacitors: "Nano's Envy, Micro's Pride"”, RSC Advances, vol. 4, pp. 15863-15869, 2014.[Abstract]


The present study provides the first reports on a low temperature molten salt route which can generate unique architecture of MnO2 nanospikes arrayed in a peculiar fashion to form micron sized ball morphology. This morphology when employed as supercapacitor electrodes gives an advantage of surface relaxation during the charge-discharge process making it super stable. The study highlights the advantages of nanostructuring of microparticles which can answer the toxicity issues and their potential as a commercial product. This claim in the present study has been validated by cell toxicity study on human dermal fibroblasts, which established that a nano/micro hybrid structure can be relatively less toxic. Cytoskeleton rearrangements were also observed as the size of MnO2 was reduced from micron to nanoscale. A mechanism of the structure formation and the influence of the salt in controlling the process parameters as well as the morphology are also proposed. These electrodes in coin cells exhibited specific mass capacitance value as high as 1100 F g -1 with a power density and energy density of 4.5 W h kg-1 and 14 kW kg-1, respectively. This journal is © the Partner Organisations 2014.

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2014

Journal Article

A. Kumar Tewari, Singh, V. Prakash, Yadav, P., Gupta, G., Singh, A., Goel, R. Kumar, Shinde, P., and Dr. Gopi Mohan C., “Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents”, Bioorganic Chemistry, vol. 56, pp. 8 - 15, 2014.[Abstract]


Abstract A novel series of pyrazole derivatives were synthesized and evaluated in vivo for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Among all compounds, 5a, and 5b showed comparable anti-inflammatory activity to Nimesulide, the standard drug taken for the studies. In silico (docking) studies were carried out to investigate the theoretical binding mode of the compounds to target the cyclooxygenase (COX-2) using Autodock 4.2. More »»

2014

Journal Article

T. G. Deepak, Anjusree, G. S., Pai, K. R. N., Subash, D., Shantikumar V Nair, and Nair, A. S., “Cabbage Leaf-shaped Two-Dimensional TiO2 Mesostructures for Efficient Dye-sensitized Solar Cells”, RSC Advances, vol. 4, pp. 27084-27090, 2014.[Abstract]


We have fabricated 'cabbage leaf'-like TiO2 mesostructures of high surface area from electrospun TiO2-SiO2 composite nanofibers by titanate route for dye-sensitized solar cell (DSC) application. The initial TiO2-SiO2 composite nanofibers, the intermediate titanate and the final leaf-like TiO2 are characterized by spectroscopy, microscopy and surface area measurements. The material (final TiO2) acts as a dual functional material in DSCs with high dye loading and a high light scattering capability. The best DSC (a square-shaped cell of area 0.20 cm2 and thickness of 12 μm) fabricated out of the material showed a superior photovoltaic performance with an efficiency (η) of 7.92% in comparison to that of commercial P25 TiO2 (6.50%). This journal is © the Partner Organisations 2014.

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2014

Journal Article

B. M. Alphonsa, Kumar, P. T. Sudheesh, Praveen, G., Dr. Raja Biswas, Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Antimicrobial drugs encapsulated in fibrin nanoparticles for treating microbial infested wounds”, Pharmaceutical Research, vol. 31, pp. 1338-1351, 2014.[Abstract]


Purpose: In vitro evaluation of antibacterial and antifungal drugs encapsulated fibrin nanoparticles to prove their potential prospect of using these nanocomponent for effective treatment of microbial infested wounds. Methods: Surfactant-free oil-in-water emulsification-diffusion method was adopted to encapsulate 1 mg/ml each of antimicrobial drugs (Ciprofloxacin and Fluconazole) in 4 ml of aqueous fibrinogen suspension and subsequent thrombin mediated cross linking to synthesize drug loaded fibrin nanoparticles. Results: Ciprofloxacin loaded fibrin nanoparticles (CFNPs) showed size range of 253∈±∈6 nm whereas that of Fluconazole loaded fibrin nanoparticles (FFNPs) was 260∈±∈10 nm. Physico chemical characterizations revealed the firm integration of antimicrobial drugs within fibrin nanoparticles. Drug release studies performed at physiological pH 7.4 showed a release of 16% ciprofloxacin and 8% of fluconazole while as the release of ciprofloxacin at alkaline pH 8.5, was 48% and that of fluconazole was 37%. The antimicrobial activity evaluations of both drug loaded systems independently showed good antibacterial activity against Escherichia coli (E.coli), Staphylococcus aureus (S. aureus) and antifungal activity against Candida albicans (C. albicans). The in vitro toxicity of the prepared drug loaded nanoparticles were further analyzed using Human dermal fibroblast cells (HDF) and showed adequate cell viability. Conclusion: The efficacies of both CFNPs and FFNPs for sustained delivery of encapsulated anti microbial drugs were evaluated in vitro suggesting its potential use for treating microbial infested wounds (diabetic foot ulcer). © 2013 Springer Science+Business Media New York.

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2014

Journal Article

P. Ragesh, Nair, S. V., and Nair, A. S., “An attempt to fabricate a photocatalytic and hydrophobic self-cleaning coating via electrospinning”, RSC Advances, vol. 4, pp. 38498-38504, 2014.[Abstract]


Fluorinated POSS (polyhedral oligomeric silsesquioxanes, F-POSS) was blended with PVDF (poly (vinylidene fluoride)/TiO2 (titanium dioxide) composite by stirring overnight and the resultant solution was electrospun to obtain F-POSS/PVDF/TiO2 micron- and nanofibers with self-cleaning capacity. The coatings were deposited on a fluorosilane-treated glass substrate and they showed both hydrophobicity and photocatalytic activity. The morphology of the fabricated coating was analysed using scanning electron microscopy and atomic force microscopy. The optical properties of the coating were studied using UV-visible spectroscopy, which gave around 65-70% transmittance with just 2% of F-POSS inclusion. Membrane stability on the substrate was checked with the nano-scratch test. The nano-scratch test indicates that the tip of the nano-indenter was unable to percolate through the membrane; rather it just ploughs around its surface, revealing the adhesion of coating and mechanical stability. The contact angle measurements showed a value of 135.5° for the F-POSS/PVDF/TiO2 coating, thus showing its hydrophobic nature. The photocatalytic effect of the membrane was checked with respect to the degradation of methyl orange dye under UV exposure. The surface roughness calculated from the AFM measurements showed that the inclusion of F-POSS into the nanofibers enhanced the surface roughness. We anticipate that the thermally and mechanically stable coating may find immense applications in many real areas like water-purification, window panels, glass modules for photovoltaic devices, etc. © the Partner Organisations 2014.

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2014

Journal Article

G. S. Anjusree, Deepak, T. G., Pai, K. R. N., Jipnomon Joseph, Arun, T. A., Nair, S. V., and Nair, A. S., “TiO2 nanoparticles @ TiO2 nanofibers-an innovative one-dimensional material for dye-sensitized solar cells”, RSC Advances, vol. 4, pp. 22941-22945, 2014.[Abstract]


We report a unique one-dimensional (1-D) morphology of TiO2 having TiO2 nanoparticles decorating the surface of TiO2 nanofibers fabricated by a simultaneous electrospinning and electrospraying technique. The composite made by both nanofibers and nanoparticles is used as a photoanode material for dye-sensitized solar cells (DSCs) which helped in overcoming the limitations associated with nanofibers and nanoparticles when employed separately. The DSC showed an excellent efficiency of 7.89% (for a square-shaped cell of area 0.2 cm2) in comparison to 6.87% for the nanoparticulate DSC and 5.21% for the nanofiber DSC (for cells of the same area and thickness) which is an impressive value when literature on DSC fabrication with 1-D nanostructures for DSCs is concerned. © 2014 the Partner Organisations.

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2014

Journal Article

R. Ta Unni, Shah, G. Aa, Snima, K. Sa, Kamath, C. Rb, Nair, S. Va, and Lakshmanan, V. - Ka, “Enhanced delivery of phyllanthus niruri nanoparticles or prostate cancer therapy”, Journal of Bionanoscience, vol. 8, pp. 101-107, 2014.[Abstract]


Prostate cancer is ranked second leading cause of cancer death, globally. Conventional treatment strategies hold very limited scope as cancer advances in grade. Treatments such as surgery, radiation therapy and chemotherapy possess adverse side effects which lead us to explore the natural products as anticancer agents. The main aim of present work is to bring together the advantages of ayurvedic formulations with that of modern nanotechnology. Phyllanthus niruri is an ayurvedic plant that has shown its potential as an effective anticancer agent in prostate cancer and its ability as an effective apoptosis inducer as well as an antimetastatic agent in cancer cells. In order to increase the bioavailability of P. niruri extract, stable nanoparticles were prepared and its effect was studied. Size analysis by DLS and SEM revealed the average size of nanoparticles prepared was 150±50 nm. In vitro haemolysis and coagulation assay confirmed the blood biocompatibility of the nanoparticles. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells with cell viability of 35% with maximum concentration in 48 hrs.The prepared nanoparticles showed a significant decrease in clonogenity and wound healing capacity. On the whole the above characteristics of P. niruri nanoparticles make it a valuable candidate for prostate cancer therapy. Copyright © 2014 American Scientific Publishers All rights reserved.

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2014

Journal Article

D. Jacob, Mini, P. A., Balakrishnan, A., Shantikumar V Nair, and Subramanian, K. R. V., “Electrochemical Behaviour of Graphene-poly (3,4-ethylenedioxythiophene) (PEDOT) Composite Electrodes for Supercapacitor Applications”, Bulletin of Materials Science, vol. 37, pp. 61-69, 2014.[Abstract]


In this paper, we report on the electrochemical characteristics of graphene-PEDOT composite electrodes. The electrodes were made of indium tin oxide (ITO) substrates by simple processes of electrophoretic deposition of graphene followed by electropolymerization of EDOT monomer. The composite electrode was obtained by electrochemical measurements, a median specific capacitance of 1410 F/g and a median area capacitance of 199 mF cm-2 at a scan rate of 40 mVs-1. The composite showed good stability characteristics after repeated scans in cyclic voltammmetry and faredmuch better than a thin film of PEDOT. The thermal stability of the composite is also much superior when compared to the polymer with a weight loss temperature of 350 °C for the composite and 250 °C for the polymer, respectively. The above electrochemical and thermal behaviours of the composite are correlated to the unique morphology of electrodeposited graphene that provides a conductive and high surface area template for electropolymerization. © Indian Academy of Sciences.

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2014

Journal Article

J. Bab c McAlvin, Padera, R. Fd, Dr. Sahadev Shankarappa, Reznor, Gbc, Kwon, A. Hfg, Chiang, H. Hbc, Yang, Jh, and Kohane, D. Sbc, “Multivesicular liposomal bupivacaine at the sciatic nerve”, Biomaterials, vol. 35, pp. 4557-4564, 2014.[Abstract]


Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240mincompared to 120minfor 0.5% (w/v) bupivacaine HCl and 210minfor 1.31% (w/v) bupivacaine HCl (same bupivacaine content as Exparel™). On histologic sections four days after injection, median inflammation scores in the Exparel™ group (2.5 of 4) were slightly higher than in groups treated with bupivacaine solutions (score 2). Myotoxicity scores in the Exparel™ group (2.5 of 6) were similar to in the 0.5% (w/v) bupivacaine HCl group (3), but significantly less than in the 1.31% (w/v) bupivacaine HCl group (5). After two weeks, inflammation from Exparel™ (score 2 of 6) was greater than from 0.5% (w/v) bupivacaine HCl (1) and similar to that from 1.31% (w/v) bupivacaine HCl (1). Myotoxicity in all three groups was not statistically significantly different. No neurotoxicity was detected in any group. Tissue reaction to Exparel™ was similar to that of 0.5% (w/v) bupivacaine HCl. Surveillance for local tissue injury will be important during future clinical evaluation. © 2014 Elsevier Ltd.

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2014

Journal Article

Sa Maya, Sarmento, Bbc d, Lakshmanan, V. - Ka, Menon, Da, and Jayakumar, Ra, “Actively targeted cetuximab conjugated γ-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells”, Journal of Biomedical Nanotechnology, vol. 10, pp. 1416-1428, 2014.[Abstract]


Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded γ-poly (glutamic acid) (γ-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-γ-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-γ-PGA NPs over DTXL-γ-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-γ-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-γ-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-γ-PGA Nps (targeted) and ICG-DTXL-γ-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-γ-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer. Copyright © 2014 American Scientific Publishers All rights reserved.

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2014

Journal Article

K. R. N. Pai, Anjusree, G. S., Deepak, T. G., Subash, D., Nair, S. V., and Nair, A. S., “High surface area TiO2 nanoparticles by a freeze-drying approach for dye-sensitized solar cells”, RSC Advances, vol. 4, pp. 36821-36827, 2014.[Abstract]


We outline a simple protocol for fabricating high surface area (∼86 m2 g-1) TiO2 nanoparticles via freeze-drying of a composite of a TiO2 precursor ((Ti(iv) isopropoxide)) and a polymer (polyester) solution. The composite upon freeze-drying results in a porous mass which on subsequent sintering results in degradation of the polymer and formation of TiO2 nanoparticles. The TiO2 particles when employed as a photoanode of dye-sensitized solar cells show an efficiency (η) of ∼7%. © the Partner Organisations 2014.

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2014

Journal Article

R. Ramachandran, Malarvizhi, G. L., Chandran, P., Gupta, N., Menon, D., Panikar, D., Nair, S., and Koyakutty, M., “A Polymer-Protein Core-shell Nanomedicine for Inhibiting Cancer Migration Followed by Photo-Triggered Killing”, Journal of Biomedical Nanotechnology, vol. 10, pp. 1401-1415, 2014.[Abstract]


Migratory capacity of cancer plays a critical role in the process of metastasis. Aberrant focal adhesions activated by the phosphorylation of Src kinase enables cancer cells to anchor on its micro-environment and migrate towards biochemically favorable niche, causing metastasis. Effective blocking of the migratory capacity of cancer cells by inhibiting protein kinases and subsequent application of cytotoxic stress may provide better therapeutic outcome. Here, we report a novel core-shell nanomedicine that inhibits cancer migration by nano-shell and impart reactive oxygen stress by laser assisted photosensitization of nano-core. For this, we have optimized a polymer-protein nanoconstruct where a photosensitizer (5,10,15, 20-tetrakis(meso-hydroxyphenyl) porphyrin (mTHPP) is loaded into poly(lactic-co-glycolic acid) (PLGA) nano-core and Src kinase inhibitor (dasatinib) is loaded into albumin nano-shell. The polymer-core was prepared by electrospray technique and albumin-shell was formed by alcohol coacervation. Transmission electron microscopy studies revealed the formation of ∼80 nm sized nano-core decorated with ∼10 nm size nano-shell. Successful incorporation of monomeric mTHPP in nano-core resulted improved photo-physical properties and singlet oxygen release under physiological conditions compared to free-mTHPP. Core-shell nanomedicine also showed dose and time dependent cellular uptake in U87MG glioma cells. Dasatinib released from nano-shell caused down regulation of phospho-Src leading to significant impairment of cancer migration and subsequent laser assisted photosensitization of nano-core resulted in the release of reactive oxygen stress leading to apoptosis of spatially confined cancer cells. In vivo studies on Wistar rats indicated the absence of any significant toxicity caused by the intravenous administration of nanomedicine. These results clearly show the advantage of core-shell nanomedicine mediated combinatorial approach for inhibiting important cancer signalling pathways togother with imparting cytotoxic stress. Copyright © 2014 American Scientific Publishers All rights reserved.

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2014

Journal Article

J. Joseph, Rajagopalan, R., Anoop, S. S., Amruthalakshmi, V., Ajay, A., Balakrishnan, A., and Shantikumar V Nair, “Shape Tailored Ni3(NO3)2(OH)4 Nano-Flakes Simulating 3-D Bouquet-like Structures for Supercapacitors: Exploring the Effect of Electrolytes on stability and Performance”, RSC Advances, vol. 4, pp. 39378-39385, 2014.[Abstract]


The present study demonstrates a novel, low temperature synthetic approach by which 3-D bouquets of nickel hydroxide nitrate were processed into high surface area electrodes for supercapacitor applications. The synthesized micro-bouquets comprised randomly arrayed microporous nanoflakes (pore size: 2-6 nm) and exhibited a surface area of 150 m2 g-1. Morphological evolution studies were performed to elucidate how surface morphology of these electrode materials affect redox reactions and their ultimate performance as a supercapacitor. The electrodes were tested in three different electrolytes, namely lithium hydroxide, potassium hydroxide and sodium hydroxide. From the detailed electrochemical analysis, an intrinsic correlation between the capacitance, internal resistance and the surface morphology was deduced and explained on the basis of relative contributions from the faradaic properties in different electrolytes. Depending on the surface morphology and electrolyte incorporated, these nano/micro-hybrid electrodes exhibited specific mass capacitance value of as high as 1380 ± 38 F g-1. Inductively coupled plasma-atomic emission spectroscopy was used to determine the electrode dissolution in the given electrolyte and the findings were co-related with the cycling stability. By employing this low cost electrode design, high stability (&gt;5000 cycles with no fading) was achieved in lithium hydroxide electrolyte. Furthermore, a working model supercapacitor in a coin cell form is also shown to exhibit peak power and energy density of 3 kW kg -1 and 800 mW h kg-1, respectively. © 2014 the Partner Organisations.

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2014

Journal Article

J. Venkatesan, Dr. Jayakumar Rangasamy, Mohandas, A., Bhatnagar, I., and Kim, S. - K., “Antimicrobial Activity of Chitosan-carbon nanotube Hydrogels”, Materials, vol. 7, pp. 3946-3955, 2014.[Abstract]


In the present study, we have prepared chitosan-carbon nanotube (Chitosan-CNT) hydrogels by the freeze-lyophilization method and examined their antimicrobial activity. Different concentrations of CNT were used in the preparation of Chitosan-CNT hydrogels. These differently concentrated CNT hydrogels were chemically characterized using Fourier Transform-Infrared Spectroscopy, Scanning Electron Microscopy and Optical microscopy. The porosity of the hydrogels were found to be >94%. Dispersion of chitosan was observed in the CNT matrix by normal photography and optical microscopy. The addition of CNT in the composite scaffold significantly reduced the water uptake ability. In order to evaluate antimicrobial activity, the serial dilution method was used towards Staphylococcus aureus, Escherichia coli and Candida tropicalis. The composite Chitosan-CNT hydrogel showed greater antimicrobial activity with increasing CNT concentration, suggesting that Chitosan-CNT hydrogel scaffold will be a promising biomaterial in biomedical applications. © 2014 by the authors.

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2014

Journal Article

S. Gupta and Dr. Gopi Mohan C., “Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening”, BioMed Research International (Hindawi), 2014.[Abstract]


In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties. More »»

2014

Journal Article

A. Anitha, Deepa, N., Chennazhi, K. P., Lakshmanan, V. - K., and Dr. Jayakumar Rangasamy, “Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment”, Biochimica et Biophysica Acta - General Subjects, vol. 1840, pp. 2730-2743, 2014.[Abstract]


Background Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. Methods CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. Results The 5-FU-TCS-NPs (size: 150 ± 40 nm, zeta potential: + 48.2 ± 5 mV) and CRC-TCS-NPs (size: 150 ± 20 nm, zeta potential: + 35.7 ± 3 mV) were proven to be compatible with blood. The in vitro drug release studies at pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72 h, unlike bare CRC and 5-FU. Conclusions To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. General significance The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases. © 2014 Elsevier B.V. All rights reserved.

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2014

Journal Article

N. Sa Rejinold, Thomas, R. Gb, Muthiah, Mc, Chennazhi, K. Pa, Park, I. - Kc, Jeong, Y. Yb, Manzoor, Ka, and Dr. Jayakumar Rangasamy, “Radio Frequency Triggered Curcumin Delivery from Thermo and pH Responsive Nanoparticles Containing Gold Nanoparticles and its in Vivo Localization Studies in an Orthotopic Breast Tumor Model”, RSC Advances, vol. 4, pp. 39408-39427, 2014.[Abstract]


Non-invasive radiofrequency (RF) electric fields as an energy source for thermal activation of nanoparticles and thereby delivering drugs within cancer cells could be a valuable addition to nano-mediated RF based cancer therapies. Utilizing the high penetration of RF waves would be useful for the controlled release of encapsulated drug molecules from smart thermo and pH responsive nanoparticles. Herein, we demonstrate that breast cancer cells could selectively internalize hemocompatible, 170 ± 20 nm sized curcumin encapsulated chitosan-graft-poly(N-vinyl caprolactam) nanoparticles containing gold nanoparticles (Au-CRC-TRC-NPs). Au-CRC-TRC-NPs were predominantly accumulated within the cytoplasm. After "optimum RF exposure" at 40 watts for 5 minutes, Au-CRC-TRC-NPs absorbed and dissipated energy as heat in the range of 42 °C, which is the lower critical solution temperature (LCST) of chitosan-graft-poly(N-vinyl caprolactam), causing controlled curcumin release and inducing apoptosis to 4T1 breast cancer cells. Further, the tumor localization studies on orthotopic breast cancer models revealed that Au-CRC-TRC-NPs could selectively accumulate at primary and secondary tumors as confirmed by in vivo live imaging followed by ex vivo tissue imaging and HPLC studies. These preclinical results throw light on their feasibility as a better tumor targetable nanomedicine for RF-assisted breast treatment modalities. © 2014 the Partner Organisations.

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2014

Journal Article

Dr. Thirugnasambandam G. Manivasagam, Magusin, P. C. M. M., Srinivasan, S., Dr. Gopi Krishnan, Kooi, B. J., and Notten, P. H. L., “Electrochemical Deuteration of Metastable MgTi alloys: An Effective Way to Inhibit Phase Segregation”, Advanced Energy Materials, vol. 4, no. 1, 2014.[Abstract]


Electrochemical deuteration of metastable Mg-Ti alloys is studied. To investigate the dynamics of deuterium atoms in the crystal host, the as-prepared hydrides are examined by means of NMR spectroscopy. Remarkably the host compound, which phase segregates upon gas phase deuteration at high temperatures, preserves its original structure during low temperature electrochemical deuteration. Deuterium atoms exchange dynamically between Mg-rich and Ti-rich sites.

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2014

Journal Article

T. G. Deepak, Subash, D., Anjusree, G. S., Pai, K. R. Narendra, Nair, S. V., and Nair, A. S., “Photovoltaic property of anatase TiO2 3-D mesoflowers”, ACS Sustainable Chemistry and Engineering, vol. 2, pp. 2772-2780, 2014.[Abstract]


We have synthesized 3-D flower-like mesostructured TiO2 from one-dimensional electrospun TiO2-SiO2 nanocomposites through a modified titanate route for dye-sensitized solar cell (DSC) application. The TiO2 3-D mesoflowers with commendable internal surface area, crystallinity, and a good light scattering property satisfy the prerequisites of a DSC photoanode material. The starting TiO2-SiO2 composite, intermediate titanate, and final 3- D mesoflowered TiO2 were characterized by spectroscopy, microscopy, and surface area measurements. A DSC employing 3-D mesoflowered TiO2 as the photoanode showed a power conversion efficiency of 8.3% which was 23% higher than that of commercial P-25 (6.37%). © 2014 American Chemical Society.

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2014

Journal Article

J. Aswathy, Seethalekshmy, N. V., Hiran, K. R., Bindhu, M. R., Manzoor, K., Shantikumar V Nair, and Menon, D., “Mn-doped Zinc Sulphide Nanocrystals for Immunofluorescent Labeling of Epidermal Growth Factor Receptors on Cells and Clinical Tumor Tissues”, Nanotechnology, vol. 25, 2014.[Abstract]


The field of molecular detection and targeted imaging has evolved considerably with the introduction of fluorescent semiconductor nanocrystals. Manganese-doped zinc sulphide nanocrystals (ZnS:Mn NCs), which are widely used in electroluminescent displays, have been explored for the first time for direct immunofluorescent (IF) labeling of clinical tumor tissues. ZnS:Mn NCs developed through a facile wet chemistry route were capped using amino acid cysteine, conjugated to streptavidin and thereafter coupled to biotinylated epidermal growth factor receptor (EGFR) antibody utilizing the streptavidin-biotin linkage. The overall conjugation yielded stable EGFR antibody conjugated ZnS:Mn NCs (EGFR ZnS:Mn NCs) with a hydrodynamic diameter of 65 ± 15 nm, and having an intense orange-red fluorescence emission at 598 nm. Specific labeling of EGF receptors on EGFR+ve A431 cells in a co-culture with EGFR-ve NIH3T3 cells was demonstrated using these nanoprobes. The primary antibody conjugated fluorescent NCs could also clearly delineate EGFR over-expressing cells on clinical tumor tissues processed by formalin fixation as well as cryopreservation with a specificity of 86% and accuracy of 88%, in comparison to immunohistochemistry. Tumor tissues labeled with EGFR ZnS:Mn NCs showed good fluorescence emission when imaged after storage even at 15 months. Thus, ZnS nanobioconjugates with dopant-dependent and stable fluorescence emission show promise as an efficient, target-specific fluorophore that would enable long term IF labeling of any antigen of interest on clinical tissues. © 2014 IOP Publishing Ltd.

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2014

Journal Article

S. A. Shankarappa, Dr. Manzoor K., and Nair, S. V., “Efficacy versus Toxicity-The Ying and Yang in Translating Nanomedicines”, Nanomaterials and Nanotechnology, vol. 4, pp. 4–23, 2014.[Abstract]


Nanomedicine, as a relatively new offshoot of nanotechnology, has presented vast opportunities in biomedical research for developing novel strategies to treat diseases. In the past decade, there has been a significant increase in in vitro and preclinical studies addressing the benefits of nanomedicines. In this commentary, we focus specifically on the efficacy- and toxicity-related translational challenges of nanocarrier-mediated systems, and briefly discuss possible strategies for addressing such issues at in vitro and preclinical stages. We address questions related specifically to the balance between toxicity and efficacy, a balance that is expected to be substantially different for nanomedicines compared to that for a free drug. Using case studies, we propose a ratiometric assessment tool to quantify the overall benefit of nanomedicine as compared to free drugs in terms of efficacy and toxicity. The overall goal of this commentary is to emphasize the strategies that promote the translation of nanomedicines, especially by learning lessons from previous translational failures of other drugs and devices, and to apply these lessons to critically assess data at the basic stages of nanomedicinal research. More »»

2014

Journal Article

T. G. Deepak, Anjusree, G. S., Pai, K. R. N., Subash, D., Nair, S. V., and Nair, A. S., “Fabrication of a dye-sensitized solar cell module using spray pyrolysis deposition of a TiO2 colloid”, RSC Advances, vol. 4, pp. 23299-23303, 2014.[Abstract]


We provide a complete illustration of dye-sensitized solar module fabrication by spray pyrolysis deposition (SPD) of a TiO2 colloid having ∼10 nm sized TiO2 nanoparticles. The process was first optimized for cell level fabrication, and the parameters (mainly the thickness) obtained from the study were subsequently used for module level fabrication. The best efficiency obtained at the cell level (area 0.2 cm2 and thickness of 12 μm) was 7.79% and that for the (12 cm × 12 cm) module was 3.2%. © 2014 the Partner Organisations.

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2014

Journal Article

S. Lilly Cyriac, Deepika, B., Pillai, B., Nair, S. V., and Subramanian, K. R. V., “Development of a new solid-state absorber material for dye-sensitized solar cell (DSSC)”, Bulletin of Materials Science, vol. 37, pp. 685–693, 2014.[Abstract]


In contrast to the conventional DSSC systems, where the dye molecules are used as light harvesting material, here a solid-state absorber was used as a sensitizer in conjunction with the dye. The materials like ZnO and Al2O3 : C, which will show optically stimulated luminescence (OSL) upon irradiation were used as extremely thin absorber layers. This novel architecture allows broader spectral absorption, an increase in photocurrent, and hence, an improved efficiency because of the mobility of the trapped electrons in the absorber material after irradiation, to the TiO2 conduction band. Nanocrystalline mesoporous TiO2 photoanodes were fabricated using these solid-state absorber materials and after irradiation, a few number of samples were co-sensitized with N719 dye. On comparing both the dye loaded photoanodes (ZnO/TiO2 and Al2O3 : C/TiO2), it can be concluded from the present studies that, the Al2O3 : C is superior to ZnO under photon irradiation. Al2O3 : C is more sensitive to photon irradiation than ZnO and hence there can be more trap centres produced in Al2O3 : C. More »»

2014

Journal Article

P. Chandran, Kavalakatt, A., Malarvizhi, G. L., Vasanthakumari, D. R. V. N., Retnakumari, A. P., Sidharthan, N., Pavithran, K., Shantikumar V Nair, and Koyakutty, M., “Epigenetics Targeted Protein-Vorinostat Nanomedicine Inducing Apoptosis in Heterogeneous Population of Primary Acute Myeloid Leukemia Cells Including Refractory and Relapsed Cases”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 10, pp. 721-732, 2014.[Abstract]


Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34+/CD38- stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having  100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. From the Clinical Editor: Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc.

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2014

Journal Article

N. Ganesh, Anusha Ashokan, R kannan, R., Chennazhi, K., Shantikumar V Nair, and Dr. Manzoor K., “Magnetic Resonance Functional Nano-hydroxyapatite Incorporated Poly(caprolactone) Composite Scaffolds for in Situ Monitoring of Bone Tissue Regeneration by MRI”, Tissue Engineering - Part A, vol. 20, pp. 2783-2794, 2014.[Abstract]


In this study, we have reported the incorporation of a multi-modal contrast agent based on hydroxyapatite nanocrystals, within a poly(caprolactone)(PCL) nanofibrous scaffold by electrospinning. The multifunctional hydroxyapatite nanoparticles (MF-nHAp) showed simultaneous contrast enhancement for three major molecular imaging techniques. In this article, the magnetic resonance (MR) contrast enhancement ability of the MF-nHAp was exploited for the purpose of potentially monitoring as well as for influencing tissue regeneration. These MF-nHAp containing PCL scaffolds were engineered in order to enhance the osteogenic potential as well as its MR functionality for their application in bone tissue engineering. The nano-composite scaffolds along with pristine PCL were evaluated physico-chemically and biologically in vitro, in the presence of human mesenchymal stem cells (hMSCs). The incorporation of 30-40 nm sized MF-nHAp within the nanofibers showed a substantial increase in scaffold strength, protein adsorption, proliferation, and osteogenic differentiation of hMSCs along with enhanced MR functionality. This preliminary study was performed to eventually exploit the MR contrast imaging capability of MF-nHAp in nanofibrous scaffolds for real-time imaging of the changes in the tissue engineered construct. © Copyright 2014, Mary Ann Liebert, Inc.

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2014

Journal Article

V. A. Ganesh, Dinachali, S. S., Jayaraman, S., Sridhar, R., Raut, H. K., Góra, A., Baji, A., Sreekumaran A Nair, and Ramakrishna, S., “One-step fabrication of robust and optically transparent slippery coatings”, RSC Advances, vol. 4, pp. 55263-55270, 2014.[Abstract]


The fabrication of lubricants-infused textured surfaces has opened up a new route towards omniphobicity. However, achieving a homogeneous thin film of lubricating material on a flat/smooth surface still remains a challenge. This work shows the successful fabrication of a thin, transparent, and homogeneous coating of perfluoropolyether (PFPE, a lubricating material) on a smooth glass surface by the electrospraying technique. The sol-gel solution for electrospraying was prepared by adding a small amount of (tridecafluoro-1,1,2,2-tetrahydrooctyl)-1-trichlorosilane (FTS) with PFPE which was subsequently electrosprayed on a glass substrate. After curing the coated samples at 80 °C, a transparent, homogeneous, and slippery coating with a low surface energy (12.5 mN m-1) was obtained. It was observed that the presence of FTS with PFPE, assisted significantly in the stacking of PFPE on the substrate resulting in the formation of smooth, uniform blended (PFPE + FTS) films. The surface nature of the blended films was characterized by spectroscopy and microscopy. The blended surface exhibited omniphobic properties. The surface contact angles and slipping angles made by water and acetone droplets were measured to be (116°, 40.8°) and (6°, 10°), respectively. Furthermore, the coating showed good optical (transmittance-91%) and mechanical properties with strong adherence to glass surfaces, thus revealing the potential for applications in windows and solar modules. © 2014 The Royal Society of Chemistry.

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2014

Journal Article

K. V. Sreelakshmi, Sasi, S., Balakrishnan, A., Sivakumar, N., A. Nair, S., Shantikumar V. Nair, and Subramanian, K. R. V., “Hybrid Composites of LiMn2O4–Graphene as Rechargeable Electrodes in Energy Storage Devices”, Energy Technology, vol. 2, no. 3, p. 257--262, 2014.[Abstract]


In this study spinel-lithium manganese oxide (LiMn2O4) powders were prepared by using a simple sol–gel method with polyvinyl alcohol (PVA), and further combined with a conductive additive, graphene, to produce a composite electrode material for improved performance. The effects of the variation in the ratios of binder (PVA) to LiMn2O4 precursor on the particle size and electrochemical behavior of the composite were studied. Particle sizes of <200 nm were obtained. An energy density of 17.36 Wh kg−1 was obtained at an operating voltage of 3.2 V for the pure LiMn2O4 sample tested against a graphene electrode. For simultaneously improving power density (current Li batteries have a low power density as a disadvantage) along with energy density, the LiMn2O4–graphene composite was chosen as an electrode material. LiMn2O4–graphene composite electrodes were prepared by electrophoretic co-deposition. The ratio of LiMn2O4–graphene composite was optimized to 1:1 during the electrode study based on its electrochemical performance. An average energy density of 30 Wh kg−1, a specific capacity of 49 mAh g−1, and an enhanced power density of 800 W kg−1 at a discharge current of 0.5 A g−1 were obtained. Discharge behavior improved evidently for tests performed on composite electrodes with increased LiMn2O4 (1:1.3 graphene/LiMn2O4). An improved average energy density of 59.6 Wh kg−1 was obtained along with a power density of 697 W kg−1. The electrodes showed good performance during study of a button cell device. Such electrodes are well suited for hybrid energy storage devices having good energy and power density and bridging the gap between batteries and supercapacitors.

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2014

Journal Article

A. Kumar Rai, Vu, T. Trang, Jihyeon, G., and Jaekook, K., “Combustion synthesis of MgFe 2 O 4/graphene nanocomposite as a high-performance negative electrode for lithium ion batteries”, Materials Characterization, vol. 95, pp. 259 - 265, 2014.[Abstract]


Abstract We present a facile and cost-effective urea-assisted auto-combustion method for synthesizing pure MgFe2O4 nanoparticle and MgFe2O4/graphene nanocomposite samples followed by annealing at 600 °C for 5 h under \{N2\} atmosphere. The X-ray diffraction pattern confirmed the single phase formation for both samples. The obtained morphology of the nanocomposite sample shows that the MgFe2O4 nanoparticles are highly dispersed on conductive graphene nanosheets with particle size in the range of 50–100 nm. When applied as an anode material, MgFe2O4/graphene nanocomposite electrode shows a high reversible charge capacity of 764.4 mAh g− 1 at 0.04 C over 60 charge/discharge cycles and in spite of that it also retained a capacity of 219.9 mAh g− 1 at high current rate of 4.2 C. The obtained result is much better than the synthesized pure MgFe2O4 nanoparticle electrode. The excellent electrochemical performance of the MgFe2O4/graphene nanocomposite electrode can be attributed to the strong favorable synergistic interaction between MgFe2O4 and reduced graphene nanosheets, which supplied a large number of accessible active sites for Li+-ion insertion and short diffusion length for both Li+ ions and electrons. In addition, the graphene nanosheets in the nanocomposite electrode provide high conductivity and accommodate the large volume expansion/contraction during cycling, resulting in high capacity and long cycling stability.

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2014

Journal Article

L. Tuan Anh, Rai, A. Kumar, Thi, T. Vu, Gim, J., Kim, S., Mathew, V., and Kim, J., “Enhanced electrochemical performance of novel K-doped Co 3 O 4 as the anode material for secondary lithium-ion batteries”, J. Mater. Chem. A, vol. 2, pp. 6966-6975, 2014.[Abstract]


K-doped Co3O4 was prepared by a solvothermal method in polyol medium{,} followed by annealing at a low temperature of 400 [degree]C for 5 h. The obtained samples were characterized by the synchrotron X-ray diffraction pattern{,} field-emission scanning electron microscopy{,} energy-dispersive X-ray spectroscopy{,} field-emission transmission electron microscopy and high-resolution transmission electron microscopy. Synchrotron XRD analysis demonstrates that the K+ ion doping caused no change in the phase structure{,} and a highly crystalline KxCo3-xO4-[small delta] (x = 0.08) powder without any impurity was obtained. When applied as the anode material{,} the K+-doped Co3O4 electrode exhibits a much better rate capability and cycling stability{,} and could retain a charge capacity of 351.3 mA h g-1 at 3 C{,} while undoped Co3O4 exhibits only 144.3 mA h g-1 at the same rate. In addition{,} the electrochemical impedance spectroscopy also reveals that the K+-doped Co3O4 electrode has the highest electronic conductivity compared to an undoped sample. However{,} the improvement in the doped sample is due to the influence of K+ ions on the increased electronic conductivity{,} diffusion efficiency{,} and kinetic properties of Co3O4 during the lithiation and delithiation process. This material shows promising potential for use in high-rate anodes for lithium-ion batteries.

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2014

Journal Article

J. Harsharaj S., Rai, A. Kumar, Young, L. Jae, Jaekook, K., and Chan-Jin, P., “Enhanced electrochemical performance of flower-like Co 3 O 4 as an anode material for high performance lithium-ion batteries”, Electrochimica Acta, vol. 146, pp. 270 - 277, 2014.[Abstract]


\{ABSTRACT\} A facile urea-assisted template-free, surfactant-less chemical co-precipitation method was used to obtain a flower-like cobalt oxide sample followed by annealing at various temperatures of 400, 500, and 600 °C for 2 h. The obtained flower-like morphology was assembled by nanorods, and the nanorods were comprised of interconnected particles with a porous structure. The changes in the surface area of the obtained flower-like Co3O4 samples were systematically examined at various temperatures and their impact on the electrochemical performances was observed. Electrochemical investigation showed that the flower-like Co3O4 samples obtained at 500 °C, showed excellent cycling stability (1536.9 mA h g−1 at 0.1 C up to 50 cycles and 1226.9 mA h g−1 at 0.5 C up to 350 cycles) and superior rate capability (845 mA h g−1 at 10 C). It is believed that the porous nature of the unique structure facilitates the penetration of the electrolyte at the electrode/electrolyte interface and provides a large space for strain buffering, which ultimately allows the present sample to achieve high rate performances.

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2014

Journal Article

J. Gim, Song, J., Nguyen, D., Alfaruqi, M. Hilmy, Kim, S., Kang, J., Rai, A. Kumar, Mathew, V., and Kim, J., “A two-step solid state synthesis of LiFePO 4/C cathode with varying carbon contents for Li-ion batteries”, Ceramics International, vol. 40, pp. 1561 - 1567, 2014.[Abstract]


Abstract Olivine structured LiFePO4/carbon composites with different amounts of carbon were prepared by a modified two-step solid-state reaction. The iron citrate used as both iron and carbon sources in the reaction resulted in the formation of carbon coatings on the olivine particles as the mixed precursors were heated at three different initial-step temperatures of 200, 300 and 400 °C followed by a second-step annealing at moderate temperatures of 700 °C. The obtained final powders with varying carbon contents were systematically analyzed by characterization techniques of thermo-gravimetric analysis, X-ray powder diffraction, field-emission scanning electron microscopy, and field-emission transmission electron microscopy prior to electrochemical testing in order to determine the structural and calcination effects on the electrochemical properties of the composites. The field-emission transmission electron microscopy images revealed that the morphology of the LiFePO4 composites consist of agglomerated particles surrounded by carbon as a conductive material. Among the prepared samples, the LiFePO4/carbon composite calcined at initial-step temperature of 300 °C showed the highest discharge capacity and the best rate capability in the voltage range of 2.5–4.2 V.

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2014

Journal Article

V. Thi Trang, Rai, A. Kumar, Jihyeon, G., and Jaekook, K., “Potassium-doped copper oxide nanoparticles synthesized by a solvothermal method as an anode material for high-performance lithium ion secondary battery”, Applied Surface Science, vol. 305, pp. 617 - 625, 2014.[Abstract]


Abstract A simple and efficient approach was developed to synthesize CuO nanoparticles with improved electrochemical performance. Potassium (K+)-doped CuO nanoparticles were synthesized by a simple and cost-effective solvothermal method followed by annealing at 500 °C for 5 h under air atmosphere. For comparison, an undoped CuO sample was also synthesized under the same conditions. X-ray diffraction analysis demonstrates that the K+ ion doping caused no change in the phase structure, and highly crystalline KxCu1−xO1−δ (x = 0.10) powder without any impurity was obtained. As an anode material for a lithium ion battery, the K+-doped CuO nanoparticle electrode exhibited better capacity retention with a reversible capacity of over 354.6 mA h g−1 for up to 30 cycles at 0.1 C, as well as a high charge capacity of 162.3 mA h g−1 at a high current rate of 3.2 C, in comparison to an undoped CuO electrode (275.9 mA h g−1 at 0.1 C and 68.9 mA h g−1 at 3.2 C). The high rate capability and better cycleability of the doped electrode can be attributed to the influence of the K+ ion nanostructure on the increased electronic conductivity, diffusion efficiency, and kinetic properties of CuO during the lithiation and delithiation process.

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2014

Journal Article

A. Kumar Rai, Gim, J., Shin, E. -chol, Seo, H. - H., Mathew, V., Mandal, K. D., Parkash, O., Lee, J. - S., and Kim, J., “Effects of praseodymium substitution on electrical properties of CaCu 3 Ti 4 O 12 ceramics”, Ceramics International, vol. 40, pp. 181 - 189, 2014.[Abstract]


Abstract Effect of praseodymium (Pr3+) substitution at Ca2+ site in calcium copper titanate, CaCu3Ti4O12 (CCTO), has been investigated. Compositions with x=0.10 and 0.20 were synthesized in the system Ca(1−3x/2)PrxCu3Ti4O12 by chemical route. Crystal structure is remained cubic. X-ray diffraction and field-emission scanning electron macrographs indicate the presence of secondary phases such as CaTiO3 and CuO. X-ray photoelectron spectroscopy suggests the substitution of Ca2+ by Pr3+/Pr4+. Low temperature admittance spectroscopy identified two deep trapping levels at 0.098 and 0.073 eV for x=0.20 and 0.078 and 0.060 eV for x=0.10. High temperature impedance spectroscopy shows that the grain boundary potential is 0.40 eV and 0.48 eV for x=0.20 and x=0.10 samples respectively. Pr3+ doping decreases dielectric loss in the bulk at low temperature but increases the dc leakage due to the lower value of grain boundary potential.

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2014

Journal Article

A. Kumar Rai, Kim, S., Gim, J., Alfaruqi, M. Hilmy, Mathew, V., and Kim, J., “Electrochemical lithium storage of a ZnFe 2 O 4/graphene nanocomposite as an anode material for rechargeable lithium ion batteries”, RSC Adv., vol. 4, pp. 47087-47095, 2014.[Abstract]


In the present work{,} a graphene-based ZnFe2O4 nanocomposite has been synthesized using urea-assisted auto combustion synthesis followed by an annealing step. Urea synthesis is attractive{,} as it can rapidly synthesize materials with a high degree of control of particle size and morphology at low cost. The microstructure images clearly show that the ZnFe2O4 nanoparticles are homogeneously anchored on the surface of the graphene nanosheets. The average nanoparticle size ranges from 25-50 nm for both samples. As anode materials for lithium ion batteries{,} the obtained nanocomposite electrode shows significantly improved lithium storage properties with a high reversible capacity{,} excellent cycling stability and higher rate capability compared to the pure ZnFe2O4 nanoparticle electrode. The enhanced electrochemical performance of the nanocomposite sample can be attributed to the synergistic interaction between the uniformly dispersed ZnFe2O4 nanoparticles and the graphene nanosheets{,} which offers a large number of accessible active sites for the fast diffusion of Li+ ions{,} low internal resistance and more importantly accommodates the large volume expansion/contraction during cycling.

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2014

Journal Article

A. Kumar Rai, Thi, T. Vu, Gim, J., Mathew, V., and Kim, J., “Co1−xFe2+xO4 (x = 0.1, 0.2) anode materials for rechargeable lithium-ion batteries”, Solid State Sciences, vol. 36, pp. 1 - 7, 2014.[Abstract]


Abstract A cobalt-poor or iron rich bicomponent mixture of Co0.9Fe2.1O4/Fe2O3 and Co0.8Fe2.2O4/Fe2O3 anode materials have been successfully prepared using simple, cost-effective, and scalable urea-assisted auto-combustion synthesis. The threshold limit of lower cobalt stoichiometry in CoFe2O4 that leads to impressive electrochemical performance was identified. The electrochemical performance shows that the Co0.9Fe2.1O4/Fe2O3 electrode exhibits high capacity and rate capability in comparison to a Co0.8Fe2.2O4/Fe2O3 electrode, and the obtained data is comparable with that reported for cobalt-rich CoFe2O4. The better rate performance of the Co0.9Fe2.1O4/Fe2O3 electrode is ascribed to its unique stoichiometry, which intimately prefers the combination of Fe2O3 with Co1−xFe2+xO4 and the high electrical conductivity. Further, the high reversible capacity in Co0.9Fe2.1O4/Fe2O3 and Co0.8Fe2.2O4/Fe2O3 electrodes is most likely attributed to the synergistic electrochemical activity of both the nanostructured materials (Co1−xFe2+xO4 and Fe2O3), reaching beyond the well-established mechanisms of charge storage in these two phases.

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2014

Journal Article

L. Singh, Mandal, K. D., Rai, U. S., and Rai, A. Kumar, “Effect of site selection on dielectric properties of Fe doped CaCu3Ti4O12 electro-ceramic synthesized by citrate nitrate gel route”, Indian Journal of Physics, vol. 88, pp. 665–670, 2014.[Abstract]


The effect of doping of Fe at Cu2+ and Ti4+ sites in calcium copper titanate, CaCu3Ti4O12, has been examined. The compositions CaCu3−xFexTi4O12 (CCFTO) and CaCu3Ti4-xFexO12 (CCTFO), (x&nbsp;=&nbsp;0.10) have been synthesized by citrate nitrate gel route. XRD analysis confirms the formation of single- phase ceramics on sintering at 900&nbsp;°C for 8&nbsp;h. Structure of CaCu3Ti4O12 does not change on doping with iron on Cu-site or Ti-site and it remains cubic. Surface morphology indicates that the average grain size is in range of 30–90&nbsp;$μ$m and 5–7&nbsp;$μ$m for systems CCFTO and CCTFO, respectively. EDX studies confirm the presence of Ca2+, Cu2+, Ti4+ and Fe3+ ions as per stoichiometry of ceramics. The grain resistance of CCTFO is higher than that of CCFTO. Values of dielectric constant ($ε$ r ) and dielectric loss (tan$δ$) of CCTFO are higher than those of CCFTO ceramic at all measured frequencies and temperatures.

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2014

Journal Article

R. Ranjusha, Sajesh, K. M., Roshny, S., Lakshmi, V., Anjali, P., Sonia, T. S., A. Nair, S., Subramanian, K. R. V., Nair, S. V., Chennazhi, K. P., and Balakrishnan, A., “Supercapacitors based on freeze dried MnO2 embedded PEDOT: PSS hybrid sponges”, Microporous and Mesoporous Materials, vol. 186, pp. 30-36, 2014.[Abstract]


The present study investigates in detail the synthesis and characterization of PEDOT: PSS/MnO2 hybrid sponge electrodes for supercapacitor/ battery applications. These hybrid sponges were prepared using freeze drying technique and showed hierarchical pores ranging from micron to nanometric size. Scanning electron microscopy-energy dispersive X-ray showed uniform dispersion of MnO2 along the PEDOT: PSS matrix. Thermo gravimetric-differential thermal analysis showed higher thermal stability for these hybrid constructs compared to PEDOT: PSS sponges. From the electrochemical studies, an intrinsic correlation between overall specific capacitance, morphology and weight percentage of MnO2 in the PEDOT: PSS matrix has been defined and explained in KOH electrolyte system. High cyclic stability was observed at the end of 2000 cycles for these hybrid sponges with less than 5 % capacitance fading. These sponges exhibit mass specific capacitance values as high as 10688 F g-1 which was found to be 35% higher compare to PEDOT: PSS sponges as obtained from Weibull statistics. The application of these electrodes was explored in a fully functional asymmetric coin cell unit where an energy and power density of 200 mWh kg-1 and 6.4 kW kg-1, was obtained, respectively. © 2013 Elsevier B.V. All rights reserved. More »»

2014

Journal Article

Va Kumar, Bansal, Ga, Patel, Ja, and Mohan, Cab Gopi, “Structure-function prediction of α2A-, α2B-, and α2C-adrenoceptors using homology model assisted antagonist binding study”, Medicinal Chemistry Research, vol. 23, pp. 735-746, 2014.[Abstract]


α2A-, α2B-, and α2C- adrenoceptors belong to the rhodopsin-like G-protein coupled receptors family. They are integral membrane proteins typified by a bundle of seven transmembrane helices. 50 % of the currently available drugs in the market target G-protein coupled receptors. Crystal structure of α2A-, α2B-, and α2C-adrenoceptors are not yet solved. We performed homology modeling of the human α2A-, α2B-, and α2C-adrenoceptor subtypes based on the crystal structure of the β2-adrenergic receptor. Molecular docking studies of five different antagonists toward these receptors revealed receptor subtype selectivity, and which in turn potentially guide in the rational design of subtype selective antagonists. Graphical Abstract: [Figure not available: see fulltext.] © 2013 Springer Science+Business Media New York. More »»

2014

Journal Article

Sa Yang, Nair, A. Sb, and Ramakrishna, Sc, “Conversion efficiency enhancement of CdS quantum dot-sensitized electrospun nanostructured TiO2 solar cells by organic dipole treatment”, Materials Letters, vol. 116, pp. 345-348, 2014.[Abstract]


Here we fabricated quantum dot-sensitized solar cells (QDSCs) based on electrospinning of unique TiO2 nanostructures and subsequent CdS QDs deposition via successive ionic layer adsorption and reaction (SILAR) followed by dipole treatment (DT). It was found that by treating with 4-methoxy benzenethiol for 24 h, an overall conversion efficiency of 1.17% was achieved under AM1.5 illumination which corresponds to a dramatic 100% enhancement compared with that of untreated cells. The significant photovoltaic improvement was attributed to the upward shifting of CdS QDs energy levels for efficient charge separation and effective electron transport in electrospun TiO 2 nanostructures which is confirmed by electrochemical impedance spectroscopy. © 2013 Elsevier B.V.

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2014

Journal Article

B. P. Timko, Arruebo, Md, Dr. Sahadev Shankarappa, McAlvin, J. B., Okonkwo, O. S., Mizrahi, B., Stefanescu, C. F., Gomez, L., Zhu, J., Zhu, A., Santamaria, J., Langer, R., and Kohane, D. S., “Near-Infrared-Actuated Devices for Remotely Controlled Drug Delivery”, Proceedings of the National Academy of Sciences of the United States of America, vol. 111, pp. 1349-1354, 2014.[Abstract]


A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained onstate drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. Implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.

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2014

Journal Article

D. Karlsson, Fallarero, A., Shinde, P., Anju, C. P., Busygin, I., Leino, R., Dr. Gopi Mohan C., and Vuorela, P., “Chemical modifications of cinchona alkaloids lead to enhanced inhibition of human butyrylcholinesterase”, Natural Product Communications, vol. 9, pp. 455-458, 2014.[Abstract]


Butyrylcholinesterase (BChE) inhibitors were identified from a collection containing cinchonine, cinchonidine and synthetic derivatives, and further characterized using cytotoxicity and molecular docking studies. The most active ones were: (10≡)-10,11-dibromo-10,11-dihydrocinchonidine (11), a competitive inhibitor with Ki = 3.45±0.39 μM, and IC 50 BChE = 9.83±0.30 μM / human (h)BChE = 34.47±4.63 and O-(trimethylsilyl)cinchonine (15), a mixed inhibitor with Kiuc = 1.73±0.46 μM and Kic = 0.85±0.26 μM, and IC 50 BChE = 0.56±0.14 μM / hBChE = 0.24±0.04. In cytotoxicity experiments, ≥80% of the cells remained viable when exposed to concentrations of up to 80 μM of both inhibitors in four different cell lines, including neurons. Due to the bulkier trimethylsilyl side group of 15, it covered the active site of hBChE better than 11 with an OH-group while not being able to fit into the active site gorge of hAChE, thus explaining the selectivity of 15 towards hBChE. More »»

2014

Journal Article

T. G. Deepak, Anjusree, G. S., S. Thomas, Arun, T. A., Nair, S. V., and A. Nair, S., “A review on materials for light scattering in dye-sensitized solar cells”, RSC Advances, vol. 4, pp. 17615-17638, 2014.[Abstract]


Dye-sensitized solar cells (DSCs) offer interesting possibilities in photovoltaics which is the technology of harvesting solar photons to generate electricity. Improving the charge transport through the metal oxide film, finding dyes with better absorption both in the visible and near IR regions of the solar spectrum and fabricating innovative materials for the scattering layer are the proposed way forward for improving the efficiency of DSCs. Light scattering is employed in dye-sensitized solar cells to improve the optical absorption of the incident light. The conventional method of light scattering in DSCs is by using a separate scattering layer consisting of large particles with diameters comparable to the wavelength of the incident light. An additional over-layer on the nanocrystalline TiO2 photoanode will encourage light scattering in DSCs especially in the red part of the solar spectrum. Different nanostructures with good dye adsorption and light scattering properties were tried as light scattering layers in DSCs. Of late, scientists have attempted to use functional materials having enhanced light scattering properties and high internal surface area as dual function materials (that is a single layer of material capable of both light absorption and scattering). This review explores theoretical aspects and materials innovation for light scattering and their application in DSCs. This journal is © the Partner Organisations 2014.

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2014

Journal Article

T. S. Sonia, Anjali, P., Roshny, S., Lakshmi, V., Ranjusha, R., Subramanian, K. R. V., Nair, S. V., and Balakrishnan, A., “Nano/micro-hybrid NiS cathodes for lithium ion batteries”, Ceramics International, vol. 40, pp. 8351-8356, 2014.[Abstract]


The present study highlights a low temperature process by which 1D stacked 3D microstructures of nickel sulfide comprised of nanospikes have been synthesized and assembled as cathodes for lithium chalcogenide batteries. These micro/nano-clusters were synthesized hydrothermally under different conditions. These clusters exhibited a surface area of 15 m2 g-1. The present study also provides the first reports on the electrochemical performance of these NiS microclusters as cathode materials in lithium fluoro-Tris- sulfonimide electrolyte for lithium ion batteries. A detailed study has been performed to elucidate how surface morphology and redox reaction behaviors underlying these electrodes impact the cyclic behavior and specific capacity. This electrode-electrolyte combination showed minimal dissolution of the electrode in the electrolyte which was confirmed by inductively coupled plasma atomic emission spectroscopy. From the electrochemical analysis performed an intrinsic correlation between the capacity, self-discharge property and the surface morphology has been deduced and explained on the basis of relative contributions from the redox reactions of nickel sulfide in lithium fluoro-Tris-sulfonimide electrolyte. A working model of lithium battery in a coin cell form is also shown exhibiting a specific capacity of 550 mAh g -1. © 2014 Elsevier Ltd and Techna Group S.r.l.

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2014

Journal Article

P. Anjali, Vani, R., Sonia, T. S., Nair, AaSreekumara, Ramakrishna, S., Ranjusha, R., Subramanian, K. R. V., Sivakumar, N., Dr. Gopi Mohan C., Nair, S. V., and Balakrishnan, A., “Cerium Doped NiO Nanoparticles: A Novel Electrode Material for High Performance Pseudocapacitor Applications”, Science of Advanced Materials, vol. 6, pp. 94-101, 2014.[Abstract]


The present study demonstrates a novel electrodeposition approach by which Ce3+ doped NiO nanoparticles coated on titanium foils can be processed into a high surface area electrode for rechargeable energy storage applications. A detailed study has been performed to elucidate how cerium substitution doping and redox reaction behaviors underlying these electrodes impact the cyclic and capacitive behavior of the electrode. These nanoparticles were synthesized via molten salt technique and exhibited particle size of &nbsp;65 nm. From the analysis of the relevant electrochemical parameters, an intrinsic correlation between the substitutional doping amount, capacitance and the internal resistance has been deduced and explained on the basis of relative contributions from the faradic properties of the Ce3+ doped NiO nanoparticles in different electrolytes of varied concentrations. These thin film electrodes exhibited specific mass capacitance value as high as 1500 Fg-1 and 1077 Fg-1 (1 Ag-1) measured from cyclic voltammetry and charge discharge curves respectively, which was found to be 5 times higher than the pristine NiO nanoparticles with a capacitance retention of &gt;70% at the end of 2000th cycle. Further, a working model button cell employing these rechargeable electrodes is also demonstrated exhibiting an energy and power density of 92 Wh Kg-1 and 10 kW Kg-1, respectively. It has been shown that electrodes based on such nanoparticles can allow significant room for improvement in the cyclic stability and performance of a hybrid capacitor/battery system.

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2014

Journal Article

G. Saravanakumar, Deepagan, V. G., Dr. Jayakumar Rangasamy, and Park, J. H., “Hyaluronic Acid-based Conjugates for Tumor-targeted Drug Delivery and Imaging”, Journal of Biomedical Nanotechnology, vol. 10, pp. 17-31, 2014.[Abstract]


In recent years, hyaluronic acid (HA) has attracted significant interest in development of drug delivery systems because of its intrinsic physicochemical and biological properties, including water solubility, viscoeleasticity, non-immunogenicity, biocompatibility, and biodegradability. In addition, HA has the ability to selectively bind specific receptors on the disease-related cells such as cancer cells and activated macrophages, followed by receptor-mediated endocytosis. Owing to these unique features, HA has been extensively used for development of the targetable carriers to deliver the therapeutic and imaging agents. In this review, we discuss the recent progress in various HA-based conjugates for cancer therapy and imaging, in which the active agents are covalently conjugated or physically encapsulated. Copyright

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2014

Journal Article

S. Uthaman, Maya, S., Dr. Jayakumar Rangasamy, Cho, C. - S., and Park, I. - K., “Carbohydrate-based Nanogels as Drug and Gene Delivery Systems”, Journal of Nanoscience and Nanotechnology, vol. 14, pp. 694-704, 2014.[Abstract]


Nanogels are hydrogels with nanometer-scale three-dimensional networks of physically or chemically cross-linked chains. Nanogels have attracted much interest in recent years for various biomedical applications such as drug delivery systems and bioimaging owing to their specific properties of size tunability and intrinsic hydrophilic surfaces. Nanogels are generally classified either as natural polymer-based or synthetic polymer-based nanogels. Natural polymer-based nanogels are considered better candidates for drug delivery than synthetic polymer-based nanogels. This review summarizes the role of natural polymer-based nanogels, especially carbohydrate-based nanogels as drug and gene delivery systems. Copyright © 2014 American Scientific Publishers All rights reserved.

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2014

Journal Article

N. Sa Binulal, Natarajan, Aa, Menon, Da, Bhaskaran, V. Kb, Mony, Ua, and Nair, S. Va, “PCL-gelatin composite nanofibers electrospun using diluted acetic acid-ethyl acetate solvent system for stem cell-based bone tissue engineering”, Journal of Biomaterials Science, Polymer Edition, vol. 25, pp. 325-340, 2014.[Abstract]


Composite nanofibrous scaffolds with various poly(ε-caprolactone) (PCL)/gelatin ratios (90:10, 80:20, 70:30, 60:40, 50:50 wt.%) were successfully electrospun using diluted acetic and ethyl acetate mixture. The effects of this solvent system on the solution properties of the composites and its electrospinning properties were investigated. Viscosity and conductivity of the solutions, with the addition of gelatin, allowed for the electrospinning of uniform nanofibers with increasing hydrophilicity and degradation. Composite nanofibers containing 30 and 40 wt.% gelatin showed an optimum combination of hydrophilicity and degradability and also maintained the structural integrity of the scaffold. Human mesenchymal stem cells (hMSCs) showed favorable interaction with and proliferation on, the composite scaffolds. hMSC proliferation was highest in the 30 and 40 wt.% gelatin containing composites. Our experimental data suggested that PCL-gelatin composite nanofibers containing 30-40 wt.% of gelatin and electrospun in diluted acetic acid-ethyl acetate mixture produced nanofiber scaffolds with optimum hydrophilicity, degradability, and bio-functionality for stem cell-based bone tissue engineering. © 2013 Taylor & Francis.

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2014

Journal Article

Girish C. M., Iyer, S., Thankappan, K., Rani, V. V. D., Gowd, G. S., Menon, D., Nair, S., and Dr. Manzoor K., “Rapid Detection of Oral Cancer using Ag-TiO2 Nanostructured Surface-enhanced Raman Spectroscopic Substrates”, Journal of Materials Chemistry B, vol. 2, pp. 989-998, 2014.[Abstract]


The unique vibrational signatures of the biochemical changes in tissue samples may enable the Raman spectroscopic detection of diseases, like cancer. However, the Raman scattering cross-section of tissues is relatively low and hence the clinical translation of such methods faces serious challenges. In this study, we report a simple and efficient surface-enhanced Raman scattering (SERS) substrate, for the rapid and label-free detection of oral cancer. Raman active silver (Ag) surfaces were created on three distinct titania (TiO 2) hierarchical nanostructures (needular, bipyramidal and leaf-like) by a process involving a hydrothermal reaction, followed by the sputter deposition of Ag nanoparticles (average size: 30 nm). The resulting SERS substrate efficiencies, measured using crystal violet (CV) as an analyte molecule, showed a highest analytical enhancement factor of ∼106, a detection limit ∼1 nM and a relative standard deviation of the Raman peak maximum of ∼13% for the nano-leafy structure. This substrate was used to analyze tissue sections of 8 oral cancer patients (squamous cell carcinoma of tongue) comprising a total of 24 normal and 32 tumor tissue sections and the recorded spectra were analyzed by principal component analysis and discriminant analysis. The tissue spectra were correctly classified into tumor and normal groups, with a diagnostic sensitivity of 100%, a specificity of 95.83% and the average processing time per patient of 15-20 min. This indicates the potential translation of the SERS method for the rapid and accurate detection of cancer. © 2014 The Royal Society of Chemistry.

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2014

Journal Article

N. S. Rejinold, Baby, T., Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Dual Drug Encapsulated Thermo-sensitive Fibrinogen-graft-poly (N-isopropyl acrylamide) Nanogels for Breast Cancer Therapy”, Colloids and Surfaces B: Biointerfaces, vol. 114, pp. 209-217, 2014.[Abstract]


5-FU/Megestrol acetate loaded fibrinogen-graft-PNIPAAm Nanogels (5-FU/Meg-fib-graft-PNIPAAm NGs) were prepared for thermo responsive drug delivery toward α5β1-integrins expressing breast cancer cells in vitro (MCF-7 cells). The 60-100nm sized fib-graft-PNIPAAm nanogels (LCST=35°C) were prepared by CaCl2 cross-linker. 5-FU/Meg-fib-graft-PNIPAAm NGs showed particle size of 165-195nm size. The drug loading efficiency with 5-FU was 60% and 70% for Meg. "Drug release was greater above the lower critical solution temperature (LCST). Above LCST, drug release system triggers apopotosis and enhance toxicity to MCF-7 cells when compared to the equivalent dose of the free drug. This effect was due to the greater uptake of the drug by MCF-7 cells". 5-FU/Meg-fib-graft-PNIPAAm NGs is portrayed here as a new combinatorial thermo-responsive drug delivery agent for breast cancer therapy

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2014

Journal Article

T. R. Arunraj, Rejinold, N. S., Mangalathillam, S., Saroj, S., Dr. Raja Biswas, Dr. Jayakumar Rangasamy, and Dr. Sabitha M., “Synthesis, Characterization and Biological Activities of Curcumin Nanospheres”, Journal of Biomedical Nanotechnology, vol. 10, pp. 238-250, 2014.[Abstract]


Curcumin is one of the most versatile compounds obtained from Curcuma longa. The major obstacle in the therapeutic use of curcumin is its aqueous solubility. To enhance its aqueous solubility and biological activities, we prepared curcumin nanospheres (CNSs) by wet milling-solvent evaporation technique without any surfactants. In this study, we have focused on the synthesis, characterization and biological effects of CNSs. DLS and SEM analyses showed 50-80 nm spherical shaped CNSs with a zeta potential of -31.65 mV. FTIR revealed that there were no structural changes to CNSs. Antibacterial and antifungal studies proved that CNSs were much more effective than curcumin against Escherichia coli, Staphylococcus aureus and Candida albicans. Antioxidant activity of CNSs showed promising result for therapeutic applications. The in vitro anti-inflammatory studies proved that CNSs possessed enhanced anti-inflammatory effect against protein denaturation. Cytotoxicity and uptake of CNSs showed more toxicity on cancer cells (T47D, MG63, A375) sparing normal HDF and IEC cell lines. Skin permeation studies showed CNSs retained at different layers of pig skin. These results give clear evidence for their use against microbial and fungal skin infections as well as cancer treatment. Copyright © 2014 American Scientific Publishers All rights reserved.

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2014

Journal Article

N. S. Rejinold, Ranjusha, R., Balakrishnan, A., Mohammed, N., and Dr. Jayakumar Rangasamy, “Gold-chitin-manganese Dioxide Ternary Composite Nanogels for Radio Frequency Assisted Cancer Therapy”, RSC Advances, vol. 4, pp. 5819-5825, 2014.[Abstract]


Gold nanoparticles (Au-NPs) based chitin-MnO2 ternary composite nanogels (ACM-TNGs) were prepared by the regeneration of chitin along with MnO2 nanorods (5-20 nm) and the incorporation of 10 nm sized Au-NPs to make "ACM-TNGs". They were characterized with FT-IR, TG, and UV spectroscopy. The SEM showed spindle shaped 200 nm sized chitin-MnO2 nanogels (chitin-MnO2 NGs), whereas ACM-TNGs had spindle sizes of 220 nm. The ACM-TNGs were compatible up to 1 mg mL-1 and showed uptake into L929, HDF, MG63, T47D and A375 cell lines without affecting the cellular morphology. ACM-TNGs showed conductivity, and heating under a radio frequency (RF) source at 100 W for 2 min. They also showed the ability to kill breast cancer cells under RF radiation at 100 W for 2 min, when compared with the chitin-MnO2 NGs. The RF assisted ablation of breast cancer cells was confirmed by a live/dead assay. These results suggests that ACM-TNGs could be useful for the RF assisted cancer cells ablation with minimal toxicity compared with MnO2 nanorods.

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2014

Journal Article

S. Narayanan, Pavithran, M., Viswanath, A., Narayanan, D., Mohan, C. C., Manzoor, K., and Menon, D., “Sequentially releasing dual-drug-loaded PLGA-casein core/shell nanomedicine: Design, synthesis, biocompatibility and pharmacokinetics”, Acta Biomaterialia, vol. 10, pp. 2112-2124, 2014.

2014

Journal Article

D. Narayanan, Anitha, A., Dr. Jayakumar Rangasamy, and Chennazhi, K. P., “PTH 1-34 Loaded Thiolated Chitosan Nanoparticles for Osteoporosis: Oral Bioavailability and Anabolic Effect on Primary Osteoblast Cells”, Journal of Biomedical Nanotechnology, vol. 10, pp. 166-178, 2014.

2014

Journal Article

S. N. Reddy, Sowmya, S., Bumgardner, J. D., Chennazhi, K. P., Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Tetracycline Nanoparticles Loaded Calcium Sulfate Composite Beads for Periodontal Management”, Biochimica et Biophysica Acta - General Subjects, vol. 1840, pp. 2080-2090, 2014.[Abstract]


<h4>Background</h4>

<p>The objective of this study was to fabricate, characterize and evaluate in vitro, an injectable calcium sulfate bone cement beads loaded with an antibiotic nanoformulation, capable of delivering antibiotic locally for the treatment of periodontal disease.</p>

<h4>Methods</h4>

<p>Tetracycline nanoparticles (Tet NPs) were prepared using an ionic gelation method and characterized using DLS, SEM, and FTIR to determine size, morphology, stability and chemical interaction of the drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP composite beads were prepared and characterized using SEM, FTIR and XRD. The drug release pattern, material properties and antibacterial activity were evaluated. In addition, protein adsorption, cytocompatibility and alkaline phosphatase activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4control were analyzed.</p>

<h4>Results</h4>

<p>Tet NPs showed a size range of 130&nbsp;±&nbsp;20&nbsp;nm and the entrapment efficiency calculated was 89%. The composite beads showed sustained drug release pattern. Further the drug release data was fitted into various kinetic models wherein the Higuchi model showed higher correlation value (R2&nbsp;=&nbsp;0.9279) as compared to other kinetic models. The composite beads showed antibacterial activity against&nbsp;Staphylococcus aureus&nbsp;and&nbsp;Escherichia coli. The presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In addition, the composite beads enhanced the ALP activity of hPDL cells.</p>

<h4>Conclusions</h4>

<p>The antibacterial and cytocompatible CaSO4-Tet NP composite beads could be beneficial in periodontal management to reduce the bacterial load at the infection site.</p>

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2014

Journal Article

T. R. Arunraj, N. Rejinold, S., N. Kumar, A., and Dr. Jayakumar Rangasamy, “Bio-responsive Chitin-poly(l-lactic acid) Composite Nanogels for Liver Cancer”, Colloids and Surfaces B: Biointerfaces, vol. 113, pp. 394-402, 2014.

2014

Journal Article

Prof. Prema Nedungadi and Raj, H., “Unsupervised word sense disambiguation for automatic essay scoring”, Smart Innovation, Systems and Technologies, vol. 27, pp. 437-443, 2014.[Abstract]


The reliability of automated essay scoring (AES) has been the subject of debate among educators. Most systems treat essays as a bag of words and evaluate them based on LSA, LDA or other means. Many also incorporate syntactic information about essays such as the number of spelling mistakes, number of words and so on. Towards this goal, a challenging problem is to correctly understand the semantics of the essay to be evaluated so as to differentiate the intended meaning of terms used in the context of a sentence. We incorporate an unsupervised word sense disambiguation (WSD) algorithm which measures similarity between sentences as a preprocessing step to our existing AES system. We evaluate the enhanced AES model with the Kaggle AES dataset of 1400 pre-scored text answers that were manually scored by two human raters. Based on kappa scores, while both models had weighted kappa scores comparable to the human raters, the model with the WSD outperformed the model without the WSD.

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PDF iconunsupervised-word-sense-disambiguation-for-automatic-essay-scoring.pdf

2014

Journal Article

N. Nataraj, Anjusree, G. S., Madhavan, A. Anish, Priyanka, P., Sankar, D., Nisha, N., Dr. Lakshmi Sumitra, Dr. Jayakumar Rangasamy, Balakrishnan, A., and Dr. Raja Biswas, “Synthesis and Anti-Staphylococcal Activity of TiO2 Nanoparticles and Nanowires in Ex Vivo Porcine Skin Model”, Journal of Biomedical Nanotechnology, vol. 10, pp. 864-870, 2014.[Abstract]


Staphylococcus aureus is one of the major causes of skin and soft tissue infections. In this study we compared the antimicrobial activity of two different TiO2 nanoformulations against Staphylococcus aureus. We synthesized TiO2 nanoparticles of 80 nm diameter and TiO2 nanowires of 100 nm diameter. Both nanoformulations possess anti-microbial activity; were non-hemolytic and cytocompatible. However, the anti-staphylococcal activity of TiO2 nanowires was better than the nanoparticles. In broth culture, growth of S. aureus was only partially inhibited by 2% and 4 wt% TiO2 nanoparticles and completely inhibited by TiO2 nanowires till 24 h. TiO2 nanowires treated S. aureus cells exhibits diminished membrane potential than nanoparticle treated cells. The anti-microbial properties of both TiO2 nanoformulations were validated using ex vivo porcine skin model which supplements the in vitro assays. Anti-bacterial activity of the TiO2 nanowires were also validated against multi drug resistant pathogenic strains of S. aureus, showing the clinical potency of the TiO2 nanowires compared to its nanoparticles.

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2014

Journal Article

S. N Rejinold, Dr. Raja Biswas, Chellan, G., and Dr. Jayakumar Rangasamy, “Multifaceted Chitin/poly (lactic-co-glycolic) Acid Composite Nanogels”, International journal of biological macromolecules, vol. 67, pp. 279–288, 2014.[Abstract]


Cyto-compatible, 80 nm sized chitin/PLGA composite nanogels (chit/PLGA-comp NGs) were prepared by regeneration method and characterized. The multifaceted chit/PLGA-comp NGs were surface modified with Au, Fe3O4, CdTe/ZnTe-QDs and umbelliferone, respectively. 185 nm sized Au-chit/PLGA-comp NGs, 170 nm sized QD-chit/PLGA-comp-NGs and 160 nm sized Fe3O4-chit/PLGA-comp-NGs showed RF heating. The QD-chit/PLGA-comp-NGs and 180 nm sized umb-chit/PLGA-comp-NGs were well uptaken by Escherichia coli, Staphylococcus aureus and Candida albicans. The chit/PLGA-comp NGs could be useful for microbial monitoring and RF application for cancer therapy. The preliminary data showed that multifaceted chit/PLGA-comp-NGs could be useful for hyperthermia for cancer treatment and microbial labelling and imaging.

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2014

Journal Article

K. T. Smitha, Sreelakshmi, M., Nisha, N., Dr. Jayakumar Rangasamy, and Dr. Raja Biswas, “Amidase encapsulated O-carboxymethyl chitosan nanoparticles for vaccine delivery”, International Journal of Biological Macromolecules, vol. 63, pp. 154-157, 2014.[Abstract]


This work reports the development of amidase encapsulated&nbsp;<em>O</em>-carboxymethyl chitosan nanoparticles (Ami-<em>O</em>-CMC NPs) of 300&nbsp;±&nbsp;50&nbsp;nm size by ionic cross-linking method. The prepared Ami-<em>O</em>-CMC NPs had an encapsulation efficiency of 55.39%. Haemolysis assay and cytotoxicity studies proved the hemocompatibility and cytocompatibility of the prepared NPs. The sustained release of Ami from the NPs is expected to prolong its immunogenicity and in turn lead to development of better protective immunity against&nbsp;<em>Staphylococcus aureus</em>&nbsp;infections.

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2014

Journal Article

A. M. Cherian, Nair, S. V., and Lakshmanan, V. - K., “The role of nanotechnology in prostate cancer theranostic applications”, Journal of Nanoscience and Nanotechnology, vol. 14, pp. 841-852, 2014.

2014

Journal Article

A. A. Madhavan, Ranjusha, R., Daya, K. C., Arun, T. A., Praveen, P., Sanosh, K. P., Subramanian, K. R. V., Nair, S. V., Nair, A. S., and Balakrishnan, A., “Molten Salt Synthesized TiO2-graphene Composites for Dye Sensitized Solar Cells Applications”, Science of Advanced Materials, vol. 6, pp. 828-834, 2014.[Abstract]


The present study demonstrates a facile approach by which TiO2-graphene nanocomposites can be processed into bulk powders via molten salt technique. A detailed study had been performed to elucidate the effect of graphene content (0.2-10 wt%) in these nanocomposites and its impact on the opto-electrical properties. From the analysis an intrinsic correlation between the graphene content and conductance of the composite has been explained on the basis of relative band gap and work function properties. Fluorescence spectroscopy measurements showed the excitonic intensity to be lower in these nanocomposites indicating that the recombination of photo-induced electrons and holes can be effectively inhibited. Conductivity measurements revealed mean specific conductance values about 15-55% higher than that of the TiO2 nanoparticles. Preliminary studies have shown that an efficiency of 5.4% could be attained by employing TiO2-graphene nanocomposites as photoanodes in dye sensitized solar cells. © 2014 by American Scientific Publishers.

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2014

Journal Article

S. T. Sebastian, Jagan, R. S., Rajagoplan, R., Paravannoor, A., Menon, L. V., Subramanian, K. R. V., Nair, S. V., and Balakrishnan, A., “Lithium-ion storage performance of camphoric carbon wrapped NiS nano/micro-hybrids”, RSC Advances, vol. 4, pp. 11673-11679, 2014.[Abstract]


Camphoric carbon wrapped NiS powders have been profitably exploited to fabricate high surface area electrodes for Li storage. The NiS morphology showed a network of interconnected nanoscale units with rod like profiles which terminated into needle-like apexes spanning diameters of about 50-80 nm. These particles were pyrolyzed using a camphoric solution to form a carbon sheath wrapping. These carbon functionalized NiS powders were processed into high-surface-area cathodes for a fully functional coin cell unit. A detailed study was performed to elucidate the effect of carbon content on the performance of these coin cells. BET surface area analysis revealed that these carbon sheathed NiS could exhibit a high surface area of 32 m2 g -1 compared to pristine powders which exhibited surface area values of 20 m2 g-1. From the analysis of relevant electrochemical parameters, an intrinsic correlation between the specific capacity, internal resistance and temperature has been deduced. Relative contributions of capacitive and diffusion-controlled processes underlying these thin-film electrodes have been mathematically modeled. These thin-film electrodes exhibited specific capacity values as high as 500 mA h g-1 as determined from charge discharge curves. The present study shows that this functional material can provide the advantages of simple processing technique, low cost, and scalability. © The Royal Society of Chemistry 2014.

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2014

Journal Article

K. G. Reddy, Deepak, T. G., Anjusree, G. S., S. Thomas, Vadukumpully, S., Subramanian, K. R. V., Nair, S. V., and Nair, A. S., “On global energy scenario, dye-sensitized solar cells and the promise of nanotechnology”, Physical Chemistry Chemical Physics, vol. 16, pp. 6838-6858, 2014.[Abstract]


One of the major problems that humanity has to face in the next 50 years is the energy crisis. The rising population, rapidly changing life styles of people, heavy industrialization and changing landscape of cities have increased energy demands, enormously. The present annual worldwide electricity consumption is 12 TW and is expected to become 24 TW by 2050, leaving a challenging deficit of 12 TW. The present energy scenario of using fossil fuels to meet the energy demand is unable to meet the increase in demand effectively, as these fossil fuel resources are non-renewable and limited. Also, they cause significant environmental hazards, like global warming and the associated climatic issues. Hence, there is an urgent necessity to adopt renewable sources of energy, which are eco-friendly and not extinguishable. Of the various renewable sources available, such as wind, tidal, geothermal, biomass, solar, etc., solar serves as the most dependable option. Solar energy is freely and abundantly available. Once installed, the maintenance cost is very low. It is eco-friendly, safely fitting into our society without any disturbance. Producing electricity from the Sun requires the installation of solar panels, which incurs a huge initial cost and requires large areas of lands for installation. This is where nanotechnology comes into the picture and serves the purpose of increasing the efficiency to higher levels, thus bringing down the overall cost for energy production. Also, emerging low-cost solar cell technologies, e.g. thin film technologies and dye-sensitized solar cells (DSCs) help to replace the use of silicon, which is expensive. Again, nanotechnological implications can be applied in these solar cells, to achieve higher efficiencies. This paper vividly deals with the various available solar cells, choosing DSCs as the most appropriate ones. The nanotechnological implications which help to improve their performance are dealt with, in detail. Additionally, the economic and ecological aspects of using nanotechnology are briefly introduced. © 2014 the Partner Organisations. More »»

2014

Journal Article

S. Thomas, Deepak, T. G., Anjusree, G. S., Arun, T. A., Nair, S. V., and Nair, A. S., “A review on counter electrode materials in dye-sensitized solar cells”, Journal of Materials Chemistry A, vol. 2, pp. 4474-4490, 2014.[Abstract]


Dye-sensitized solar cells (DSCs) present promising low-cost alternatives to the conventional silicon (Si)-based solar cells. A DSC consists of several components, the most prominent being a titanium dioxide/metal oxide-based photoanode, a dye, an electrolyte and a counter electrode. The photoexcited electrons from the dye diffuse through the TiO2 network in the photoanode and go to the counter electrode which generally consists of platinum (Pt) sputtered onto a fluorine-doped tin oxide (FTO) plate. The Pt in the counter electrode helps in the regeneration of dyes by catalysing the I - regeneration from the I3 - species in the redox couple. The morphology of Pt, its surface roughness, nature of the exposed facet, etc. play a crucial role in determining the overall efficiency of a DSC device. With Pt being a costly noble metal, reasonable efforts have been made to find cheaper alternatives. The review presented below gives a succinct summary of the materials in use as counter electrodes in DSCs, with a conclusion and future prospects section. More »»

2014

Journal Article

K. S. Snima, Arunkumar, P., Dr. Jayakumar Rangasamy, and Lakshmanan, V. - K., “Silymarin Encapsulated Poly(D,L-lactic-co-glycolic acid) Nanoparticles: A Prospective Candidate for Prostate Cancer Therapy”, Journal of Biomedical Nanotechnology, vol. 10, pp. 559-570, 2014.[Abstract]


Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co- glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy.

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2014

Journal Article

T. A. Arun, Madhavan, A. A., Chacko, D. K., Anjusree, G. S., Deepak, T. G., S. Thomas, Nair, S. V., and Nair, A. S., “A facile approach for high surface area electrospun TiO2 nanostructures for photovoltaic and photocatalytic applications”, Dalton Transactions, vol. 43, pp. 4830-4837, 2014.[Abstract]


A rice-shaped TiO2-ZnO composite was prepared by electrospinning a mixture comprising the precursors of TiO2 and ZnO in polyvinyl acetate polymer dissolved in N,N-dimethyl acetamide. The electrospun nanofibers upon heat treatment in air resulted in collapse of the continuous fiber morphology and the formation of the rice-shaped TiO2-ZnO composite. The TiO2-ZnO composite was then treated with dilute acetic acid under hydrothermal conditions to etch ZnO from the TiO2-ZnO composite to get coral-shaped anisotropic TiO2. The structural anisotropy of TiO2 produced by the selective etching of ZnO resulted in a high surface area of 148 m2 g-1 for the TiO2. The initial and final materials were characterized by scanning electron microscopy, transmission electron microscopy, Raman and XPS spectroscopies, powder X-ray diffraction and BET surface area measurements. The utility of the anisotropic TiO2 in photovoltaics and photocatalysis was explored. Dye-sensitized solar cells fabricated using the TiO2 showed a conversion efficiency of 6.54% as against 4.8% for a control experiment with the rice-shaped TiO 2. The anisotropic TiO2 also showed good photocatalysis in the degradation of methyl orange dye and phenol. More »»

2014

Journal Article

E. Elizabeth, Baranwal, G., Krishnan, A. G., Menon, D., and Dr. Manitha B. Nair, “ZnO nanoparticle incorporated nanostructured metallic titanium for increased mesenchymal stem cell response and antibacterial activity”, Nanotechnology, vol. 25, 2014.[Abstract]


Recent trends in titanium implants are towards the development of nanoscale topographies that mimic the nanoscale properties of bone tissue. Although the nanosurface promotes the integration of osteoblast cells, infection related problems can also occur, leading to implant failure. Therefore it is imperative to reduce bacterial adhesion on an implant surface, either with or without the use of drugs/antibacterial agents. Herein, we have investigated two different aspects of Ti surfaces in inhibiting bacterial adhesion and concurrently promoting mammalian cell adhesion. These include (i) the type of nanoscale topography (Titania nanotube (TNT) and Titania nanoleaf (TNL)) and (ii) the presence of an antibacterial agent like zinc oxide nanoparticles (ZnOnp) on Ti nanosurfaces. To address this, periodically arranged TNT (80-120 nm) and non-periodically arranged TNL surfaces were generated by the anodization and hydrothermal techniques respectively, and incorporated with ZnOnp of different concentrations (375 μM, 750 μM, 1.125 mM and 1.5 mM). Interestingly, TNL surfaces decreased the adherence of staphylococcus aureus while increasing the adhesion and viability of human osteosarcoma MG63 cell line and human mesenchymal stem cells, even in the absence of ZnOnp. In contrast, TNT surfaces exhibited an increased bacterial and mammalian cell adhesion. The influence of ZnOnp on these surfaces in altering the bacterial and cell adhesion was found to be concentration dependent, with an optimal range of 375-750 μM. Above 750 μM, although bacterial adhesion was reduced, cellular viability was considerably affected. Thus our study helps us to infer that nanoscale topography by itself or its combination with an optimal concentration of antibacterial ZnOnp would provide a differential cell behavior and thereby a desirable biological response, facilitating the long term success of an implant. More »»

2014

Journal Article

A. Anitha, Sowmya, S., Kumar, P. T. S., Deepthi, S., Chennazhi, K. P., Ehrlich, H., Tsurkan, M., and Dr. Jayakumar Rangasamy, “Chitin and Chitosan in Selected BiomedicalApplications”, Progress in Polymer Science, vol. 39, pp. 1644-1667, 2014.[Abstract]


Chitin (CT), the well-known natural biopolymer and chitosan (CS) (bio-based or "artificial polymer") are non-toxic, biodegradable and biocompatible in nature. The advantages of these biomaterials are such that, they can be easily processed into different forms such as membranes, sponges, gels, scaffolds, microparticles, nanoparticles and nanofibers for a variety of biomedical applications such as drug delivery, gene therapy, tissue engineering and wound healing. Present review focuses on the diverse applications of CT and CS membranes and scaffolds for drug delivery, tissue engineering and targeted regenerative medicine. The chitinous scaffolds of marine sponges' origin are discussed here for the first time. These CT based scaffolds obtained from Porifera possess remarkable and unique properties such as hydration, interconnected channels and diverse structural architecture. This review will provide a brief overview of CT and CS membranes and scaffolds toward different kinds of delivery applications such as anticancer drug delivery, osteogenic drug delivery, and growth factor delivery, because of their inimitable release behavior, degradation profile, mucoadhesive nature, etc. The review also provides an overview of the key features of CT and CS membranes and scaffolds such as their biodegradability, cytocompatibility and mechanical properties toward applications in tissue engineering and wound healing.

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2014

Journal Article

T. A. Arun, Chacko, D. K., Madhavan, A. A., Deepak, T. G., Anjusree, G. S., Sara, T., Ramakrishna, S., Nair, S. V., and A. Nair, S., “Flower-shaped anatase TiO2 mesostructures with excellent photocatalytic properties”, RSC Advances, vol. 4, pp. 1421-1424, 2014.[Abstract]


The present paper reports a simple route to fabricate high surface area anatase TiO2 mesoflowers from electrospun TiO2-SiO 2 composite nanostructures. Electrospun fiber- and rice-shaped TiO2-SiO2 composite nanostructures upon treatment with concentrated alkali (NaOH) under hydrothermal conditions (180°C) result in chemical transformation of the TiO2 and in situ etching of SiO 2 to give sodium titanates. The sodium titanate upon acidification followed by a low temperature sintering (180°C) results in 3D TiO 2 mesoflowers. The material is found to be superior to the commercial P-25 in photocatalysis. © 2014 The Royal Society of Chemistry. More »»

2014

Journal Article

Ra Jayakumar, Khandare, Jb, Calderón, Mc, and Perumal, Od, “A special issue on polymer conjugate based nanotherapeutics”, Journal of Biomedical Nanotechnology, vol. 10, pp. 1-3, 2014.

2014

Journal Article

A. Kumar, Sreehari, S., Velayudhan, K., Dr. Lalitha Biswas, Babu, R., Ahmed, S., Sharma, N., Kurupath, V. P., Jojo, A., Dinesh, K. R., Karim, S., and Biswas, R., “Autochthonous Blastomycosis of the Adrenal: First Case Report from Asia”, The American Journal of Tropical Medicine and Hygiene, vol. 90, 2014.

2014

Journal Article

N. Nair, Biswas, R., Götz, F., and Dr. Lalitha Biswas, “Impact of Staphylococcus aureus on Pathogenesis in Polymicrobial Infections”, Infection and Immunity, vol. 82, pp. 2162–2169, 2014.[Abstract]


Polymicrobial infections involving Staphylococcus aureus exhibit enhanced disease severity and morbidity. We reviewed the nature of polymicrobial interactions between S. aureus and other bacterial, fungal, and viral cocolonizers. Microbes that were frequently recovered from the infection site with S. aureus are Haemophilus influenzae, Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus pneumoniae, Corynebacterium sp., Lactobacillus sp., Candida albicans, and influenza virus. Detailed analyses of several in vitro and in vivo observations demonstrate that S. aureus exhibits cooperative relations with C. albicans, E. faecalis, H. influenzae, and influenza virus and competitive relations with P. aeruginosa, Streptococcus pneumoniae, Lactobacillus sp., and Corynebacterium sp. Interactions of both types influence changes in S. aureus that alter its characteristics in terms of colony formation, protein expression, pathogenicity, and antibiotic susceptibility.

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2014

Journal Article

K. S. Snima, Dr. Jayakumar Rangasamy, and Lakshmanan, V. - K., “In vitro and in vivo biological evaluation of O-carboxymethyl chitosan encapsulated metformin nanoparticles for pancreatic cancer therapy”, Pharmaceutical research, vol. 31, pp. 3361–3370, 2014.[Abstract]


Purpose

In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy.

Methods

In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs.

Results

In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs.

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2014

Journal Article

W. Xavier, Sukumaran, M. T., Varma, A. Kumar, Kumar, H., and Chellan, G., “Emergence of Multi Drug Resistant Bacteria in Diabetic Patients with Lower Limb Wounds”, The Indian journal of medical research, vol. 140, p. 435, 2014.

2014

Journal Article

S. Maya, Sarmento, B., Lakshmanan, V. - K., Menon, D., and Dr. Jayakumar Rangasamy, “Actively Targeted Cetuximab Conjugated $\gamma$-poly (glutamic acid)-docetaxel Nanomedicines for Epidermal Growth Factor Receptor Over Expressing Colon Cancer Cells”, Journal of biomedical nanotechnology, vol. 10, pp. 1416–1428, 2014.[Abstract]


Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded γ-poly (glutamic acid) (γ-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-γ-PGA Nps by HT-29 (EGFR+ ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-γ-PGA NPs over DTXL-γ-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-γ-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-γ-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-γ-PGA Nps (targeted) and ICG-DTXL-γ-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-γ-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer.

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2014

Journal Article

M. Sreerenganathan, Mony, U., and Dr. Jayakumar Rangasamy, “Thermo-responsive Fibrinogen Nanogels: a Viable Thermo-responsive Drug Delivery Agent for Breast Cancer Therapy?”, Nanomedicine, vol. 9, pp. 2721–2723, 2014.[Abstract]


Breast cancer is reported to be the most frequent cancer type in women worldwide, with approximately 1.7 million newly diagnosed cases reported in 2012. During their lifetime, approximately 12% of women in the USA will develop invasive breast cancer, the second leading cause of cancer death of women in the USA [1]. In India, 1000,000 new cases of breast cancer are being reported every year [2]. Both local and systemic therapies are available for breast cancer now. Current treatment methods for breast cancer include invasive surgical procedures, radiotherapy, hormone therapy and chemotherapy. These therapies are less effective and recurrence is still a major problem in breast cancer patients. These therapies impart severe side effects and significant toxicity to normal cells [3]. A minimally invasive local delivery system capable of delivering one or a combination of drugs may overcome risks associated with surgery and also reduce the toxicity of anticancer drugs to normal cells/tissues.

Nanogel holds promise as one of the best drug-delivery systems owing to its water solubility, biocompatibility, excellent encapsulation stability and ease to synthesize. Nanogels also respond well to biological stimuli. Various possibilities of using nanogels exist in cancer therapeutics as unlike other commonly available cancer chemotherapeutic drugs used in the clinic, which target cancer cells from outside, nanogels can be effectively used to functionalize with ligands and that in turn helps in cancer cell targeting [4–6].

For carrying therapeutic moieties for cancer, the usage of macromolecules such as fibrin and fibrinogen are gaining interest nowadays. Fibrin glue has been exploited in carrying methotraxate, which showed considerable potential in shrinking tumors in glioblastoma in vivo. Fibrinogen-bound methotrexate therapy in vivo was described for Gardner lymphosarcoma in mice. Fibrinogen-methotrexate conjugate showed significant in vivo anti-tumor activity compared with that of free methotrexate and thus suggested the therapeutic utility of these potential drug conjugates [7]. Jakate et al. reported docetaxel-loaded olive oil droplet coated with fibrinogen useful for taxane-sensitive fibrin-rich tumors by facilitating the retention of these droplets in the tumor microenvironment. They reported improvement in the median survival time of B16F10 melanoma bearing mice compared with the free taxotere treatment [8].

In the last few years, many researchers have reported the use of this nanoformulated natural protein as a drug cargo for cancer. Sanoj et al. (2010) reported the fabrication of biocompatible fibrinogen nanoparticle (FNP) using simple co-acervation method. The 150 nm-sized fibrinogen nanoparticles was taken up efficiently by the cancer cells and nontoxic to an array of cancer and normal cell lines. FNPs were also found to be hemocompatible and biocompatible in vitro [9].

These fibrinogen nanoparticles were used for delivering anticancer agents like curcumin (CRC), a potent phytochemical and 5-flurouracil (5-FU), a pyramidine analog. CRC-FNPs and 5-FU-FNPs exhibited controlled and sustained release of these drugs in vitro and induced toxicity toward breast cancer cell lines (MCF-7). The tumor-accumulating property of fibrinogen is utilized and hence advantageous for delivering these anticancer therapeutic agents [10,11]. There are reports regarding the peptides binding to the irradiated tumor microvasculature and hence conjugation of these peptides to various carrier systems aid in tumor targeted drug delivery. The affinity of fibrinogen to integrin receptors has been studied in B16F0 tumors. Fibrinogen nanoparticles and liposomes were found to selectively bind within irradiated tumor blood vessels. The study reported the binding of fibrinogen-conjugated nanoparticles to radiation-activated receptors, reduced tumor blood flow and showed significant delayed and regressed tumor growth [12,13]. The above-mentioned micronized olive oil droplet with docetaxel and fibrinogen coating was also found to be effective against TA3/St mammary tumor grown in ascites [8].

Now researchers are thinking of stimuli-sensitive nanosystems for the efficient release of drugs to the target. Nanogels containing water within their structures hold promise in biomedical applications due to their responsiveness to temperature [13,14]. Fibrinogen was again exploited in thermo-responsive delivery of breast cancer drugs like megestrol acetate (Meg) in targeted fashion. Thermo-responsive polymer-like poly(N-isopropylacrylamide) (PNIPAAm) with a lower critical solution temperature (LCST) in the range of 30–32°C was grafted with fibrinogen and nanoformulated into nanogels with a combination of 5-FU/Meg drugs loaded within. Here the affinity of fibrinogen to interact with α5β1Integrin receptors overexpressed on various cancer cells including breast cancer cells has been reported. Thus 5-FU/Meg-loaded-fib-graft-PNIPAAm NGs preferentially target and deliver the therapeutic agents to breast cancer cells. Similarly, fibrinogen-graft-Poly(N-vinyl caprolactam) loaded with these dual drugs were reported to have efficient delivery properties toward breast cancer cells in vitro [15,16].

Fibrinogen-based nanosystems can be utilized not only for therapy but also for imaging purposes as well. A multifunctional fibrinogen nanoparticle was reported by Sanoj et al. for simultaneous therapy and imaging of breast cancer cells in vitro [17]. They have loaded a potent chemotherapeutic agent paclitaxel to fibrinogen-coated CdTe/ZnTe quantum dots (QDs) that aid in cancer cell imaging. Fibrinogen coating has significantly reduced the toxicity induced by the bare QDs which make it more cytocompatible and also provide α5β1Integrin receptor targeting to breast cancer cells. α5β1 +ve cancer cells like MCF-7 and Hela cells showed significant localization of these fibrinogen-coated-QDs compared with that of α5β1-ve L929 and HT-29 cells. So the synthesized paclitaxel-fibrinogen-coated yellow QDs were reported to have a bifunctional, imaging and therapeutic effect on breast cancer cells [17].

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2014

Journal Article

S. Maya, Sarmento, B., Lakshmanan, V. - K., Menon, D., Seabra, V., and Dr. Jayakumar Rangasamy, “Chitosan Cross-linked Docetaxel Loaded EGF Receptor Targeted Nanoparticles for Lung Cancer Cells”, International journal of biological macromolecules, vol. 69, pp. 532–541, 2014.[Abstract]


Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR −ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds.

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2014

Journal Article

N. Ashwinkumar, Maya, S., and Jayakumar, R., “Redox-responsive cystamine conjugated chitin–hyaluronic acid composite nanogels”, RSC Advances, vol. 4, pp. 49547–49555, 2014.[Abstract]


Nanoscale carriers were developed to overcome the challenging barriers for the targeted intracellular delivery of chemotherapeutic agents, in particular within tumors. We demonstrate redox responsive cystamine (Cys) conjugated hyaluronic acid (HA)–chitin (CNG) nanogels for the intracellular delivery of doxorubicin (DOX) within colon cancer cells. Chitin, having a slow degrading property, could make HA to slowly degrade, thus protecting the DOX from a sudden burst release, and HA, being a ligand for the CD44 receptor, are over expressed in colon cancer cells (HT-29). 150–200 nm sized DOX-HA-CNGs and DOX-HA-Cys-CNGs were developed and characterized by DLS, Zeta, TG/DTA, FT-IR, EDAX and rheological techniques. The composite nanogel preparations proved to be safe for intravenous administration because they were non-hemolytic and did not interfere with the coagulation cascade. Flow cytometric and fluorescent microscopic analysis proved the specific internalization of DOX-HA-CNGs within HT-29 cells (CD-44 +ve). MTT assay revealed the superior anti-proliferative activity of DOX-HA-Cys-CNGs in CD-44 +ve HT-29 cells compared to that in CD-44 −ve IEC-6 cells. Thus, HA-Cys-CNGs are proven to be a better carrier for the selective, redox responsive and intracellular delivery of DOX. More »»

2014

Journal Article

K. Sreenivasa Snima, Pillai, P., Cherian, A. Mary, Nair, S. V., and Lakshmanan, V. - K., “Anti-diabetic drug metformin: challenges and perspectives for cancer therapy”, Current cancer drug targets, vol. 14, pp. 727–736, 2014.[Abstract]


Metformin, a biguanide, is a commonly administered drug for the management of type 2 diabetes mellitus. The drug received tremendous recognition, when retrospective studies proved metformin-associated reduction in cancer risk. Metformin has potential anticancer effects and an ability to suppress tumor growth both in vitro and in vivo. Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin. Nanotechnology approaches have also been adopted for metformin delivery to cancer cells. This review directs on the application of metformin for the therapy of various cancers and also the different pathways responsible for the metformin derived anticancer effect. It also focuses on the pharmacological applications of metformin and the nanotechnology approaches for metformin delivery. More »»

2014

Journal Article

Dr. Jayakumar Rangasamy, T, S. Kumar. P., G, P., Raj, M., and P, C. K., “Flexible, Micro-Porous Chitosan-Gelatin Hydrogel/Nano Fibrin Composite Bandages for Treating Burn Wounds”, vol. 4, no. 110, 2014.[Abstract]


We developed chitosan–gelatin hydrogel/nanofibrin ternary composite bandages for the treatment of burn wounds and characterized the material by SEM. The spherical nanofibrin moieties (229 ± 3 nm in size) were prepared using an emulsification method and were distributed within the chitosan–gelatin matrix. The presence of the fibrin component within the matrix was confirmed by SEM and phosphotungstic acid-hematoxylin staining. The swelling, biodegradation, porosity, whole-blood clotting, platelet activation, cell viability, cell attachment and cell infiltration properties of the nanocomposite bandages were evaluated. The nanocomposite bandages were flexible, degradable and showed enhanced blood clotting and platelet activity compared with control samples. The nanocomposite bandages showed adequate swelling ability when immersed in water and phosphate-buffered saline. Cell viability studies on normal human dermal fibroblast and human umbilical cord vein endothelial cells proved the non-toxic nature of the composite bandages. Cell attachment and infiltration studies showed that the human dermal fibroblast and human umbilical cord vein endothelial cells attached to the bandage. Enhanced collagen deposition and re-epithelialization with the formation of intact mature epidermis was noted in the animal groups treated with the nanocomposite bandages compared with the experimental controls. These results show that these ternary nanocomposite bandages are ideal candidates for burn wound dressings.

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2014

Journal Article

S. Maehiro, Takeuchi, A., Yamashita, J., Hiraki, T., Kawabata, Y., Nakasone, K., Hosono, K., Usami, T., Dr. Bindhu Paul, Nagahama, Y., Oka, Y., and Okubo, K., “Sexually dimorphic expression of the sex chromosome-linked genes cntfa and pdlim3a in the medaka brain”, Biochemical and Biophysical Research Communications, vol. 445, pp. 113 - 119, 2014.[Abstract]


Abstract In vertebrates, sex differences in the brain have been attributed to differences in gonadal hormone secretion; however, recent evidence in mammals and birds shows that sex chromosome-linked genes, independent of gonadal hormones, also mediate sex differences in the brain. In this study, we searched for genes that were differentially expressed between the sexes in the brain of a teleost fish, medaka (Oryzias latipes), and identified two sex chromosome genes with male-biased expression, cntfa (encoding ciliary neurotrophic factor a) and pdlim3a (encoding \{PDZ\} and \{LIM\} domain 3 a). These genes were found to be located 3–4 Mb from and on opposite sides of the Y chromosome-specific region containing the sex-determining gene (the medaka X and Y chromosomes are genetically identical, differing only in this region). The male-biased expression of both genes was evident prior to the onset of sexual maturity. Sex-reversed \{XY\} females, as well as wild-type \{XY\} males, had more pronounced expression of these genes than \{XX\} males and \{XX\} females, indicating that the Y allele confers higher expression than the X allele for both genes. In addition, their expression was affected to some extent by sex steroid hormones, thereby possibly serving as focal points of the crosstalk between the genetic and hormonal pathways underlying brain sex differences. Given that sex chromosomes of lower vertebrates, including teleost fish, have evolved independently in different genera or species, sex chromosome genes with sexually dimorphic expression in the brain may contribute to genus- or species-specific sex differences in a variety of traits.

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2014

Journal Article

Dr. Bindhu Paul, Bhandari, R. K., Kobayashi, T., Horiguchi, R., Kobayashi, Y., Nakamoto, M., Shibata, Y., Sakai, F., Nakamura, M., and Nagahama, Y., “ERRATUM: Estrogen oversees the maintenance of the female genetic program in terminally differentiated gonochorists”, Scientific reports, vol. 4, 2014.[Abstract]


The sexual plasticity of the gonads is not retained after the completion of sex differentiation in vertebrates, except in some hermaphroditic species. Here, we report that the depletion of estradiol-17β (E2) by aromatase inhibitors (AI) for up to six months resulted in a functional female-to-male sex reversal in sexually-mature adults of two gonochoristic fish species, Nile tilapia and medaka. The sex-reversed fish showed a typical male pattern of E2 and androgen levels, secondary sexual characteristics, and male-like sex behavior, producing fertile sperm. Conversely, co-treatment of E2 inhibited AI-induced sex reversal. In situ hybridization of medaka gonads during AI-induced sex reversal indicated that cysts on the dorsal side of the adult ovaries are the origin of germ cells and Sertoli cells in the newly formed testicular tissue. Gonochoristic fish maintain their sexual plasticity until adulthood and E2 plays a critical role in maintaining the female phenotype. More »»

2014

Journal Article

V. Sukhithasri, Vinod, V., Varma, S., and Dr. Raja Biswas, “Mycobacterium tuberculosis treatment modalities and recent insights”, Current drug delivery, vol. 11, pp. 744–752, 2014.[Abstract]


Antimicrobial therapy of infections caused by M. tuberculosis is a challenge due to poor response to therapy and recurrent infections. Under in vitro conditions, antibiotics effectively kill M. tuberculosis within the first two weeks. However, an extended treatment time of 6-9 months is required to eradicate M. tuberculosis infection, mainly due to the intracellular survival of this pathogen and poor penetration of the antibiotics into the intracellular compartment of the host cells. Recent advances in the field of drug delivery have led to the use of different antibiotic incorporated nano- and micro- formulations such as liposomes, polymeric particles, mesoporous silica particles and particulate suspensions for targeted drug delivery applications into the intracellular compartment of the macrophages. The drug incorporated nano- and micro-particles are prone to be easily internalized, which leads to preferential delivery of the drugs into the tissues and organs of interest. Other advantages of these nano- and micro-particles over the free drugs are their comparatively higher stability and bioavailability. This review highlights the current strategies and challenges in treatment, the different antibiotics available, their modes of action, generation and mechanism of drug resistance and recent advances in the intracellular drug delivery using nanoparticles for the treatment of tuberculosis. More »»

2014

Journal Article

N. Nair, Dr. Raja Biswas, Götz, F., and Biswas, L., “Staphylococcus aureus in polymicrobial infections: impact on pathogenesis”, Infection and Immunity, p. IAI–00059, 2014.[Abstract]


Polymicrobial infections involving S. aureus exhibit enhanced disease severity and morbidity. We reviewed the nature of polymicrobial interactions between S. aureus and other bacterial, fungal and viral co-colonizers. Microbes that were frequently recovered from the infection site with S. aureus are Haemophilus influenzae, Enterococcus faecalis, P. aeruginosa, S. pneumoniae, Corynebacterium sp, Lactobacillus sp, Candida albicans and influenza virus. Detailed analysis of several in vitro and in vivo observations demonstrate that S. aureus exhibits cooperative relations with C. albicans, E. faecalis, H. influenzae and influenza virus and competitive relations with P. aeruginosa, Streptococcus pneumoniae, Lactobacillus sp, and Corynebacterium sp. Both of these interactions influence changes in S. aureus that alter its characteristics in terms of colony formation, protein expressions, pathogenicity and antibiotic susceptibility. More »»

2014

Journal Article

Dr. Manitha B. Nair and Krishnan, A., “Antibiotic releasing biodegradable scaffolds for osteomyelitis”, Current drug delivery, vol. 11, pp. 687–700, 2014.[Abstract]


Osteomyelitis is characterized by progressive inflammatory bone degeneration. In the management of chronic osteomyelitis, it is necessary to remove the infected bone tissue followed by implantation of an antibiotic releasing biomaterial that can release antibiotic locally for long periods of time. The main carrier used in clinics for this application is polymethylmethacrylate (PMMA) (Eg. Septopal beads). However, major drawback is the need of an additional surgery to remove the beads after therapy, as PMMA is not biodegradable. This necessitates the requirement of biodegradable carrier systems that can release antibiotics and simultaneously support debrided bone formation. This review summarizes biodegradable carrier systems that have been reported for the localised treatment and prophylaxis of osteomyelitis.

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2014

Journal Article

B. NS, A, N., Menon, D., ,, Mony, U., and Nair, S. V., “PCL-gelatin composite nanofibers electrospun using diluted acetic acid-ethyl acetate solvent system for stem cell-based bone tissue engineering.”, J Biomater Sci Polym Ed. , vol. 25, no. 4, pp. 325-40, 2014.[Abstract]


Composite nanofibrous scaffolds with various poly(ε-caprolactone) (PCL)/gelatin ratios (90:10, 80:20, 70:30, 60:40, 50:50 wt.%) were successfully electrospun using diluted acetic and ethyl acetate mixture. The effects of this solvent system on the solution properties of the composites and its electrospinning properties were investigated. Viscosity and conductivity of the solutions, with the addition of gelatin, allowed for the electrospinning of uniform nanofibers with increasing hydrophilicity and degradation. Composite nanofibers containing 30 and 40 wt.% gelatin showed an optimum combination of hydrophilicity and degradability and also maintained the structural integrity of the scaffold. Human mesenchymal stem cells (hMSCs) showed favorable interaction with and proliferation on, the composite scaffolds. hMSC proliferation was highest in the 30 and 40 wt.% gelatin containing composites. Our experimental data suggested that PCL-gelatin composite nanofibers containing 30-40 wt.% of gelatin and electrospun in diluted acetic acid-ethyl acetate mixture produced nanofiber scaffolds with optimum hydrophilicity, degradability, and bio-functionality for stem cell-based bone tissue engineering.

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2014

Journal Article

V. Kumar, Bansal, G., Patel, J., and Dr. Gopi Mohan C., “Structure–Function Prediction of $\alpha$2A-, $\alpha$2B-, and $\alpha$2C-Adrenoceptors using Homology Model Assisted Antagonist Binding Study”, Medicinal Chemistry Research, vol. 23, pp. 735–746, 2014.[Abstract]


$\alpha$2A-, $\alpha$2B-, and $\alpha$2C-adrenoceptors belong to the rhodopsin-like G-protein coupled receptors family. They are integral membrane proteins typified by a bundle of seven transmembrane helices. 50&nbsp;{%} of the currently available drugs in the market target G-protein coupled receptors. Crystal structure of $\alpha$2A-, $\alpha$2B-, and $\alpha$2C-adrenoceptors are not yet solved. We performed homology modeling of the human $\alpha$2A-, $\alpha$2B-, and $\alpha$2C-adrenoceptor subtypes based on the crystal structure of the $\beta$2-adrenergic receptor. Molecular docking studies of five different antagonists toward these receptors revealed receptor subtype selectivity, and which in turn potentially guide in the rational design of subtype selective antagonists.

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2014

Journal Article

Dr. Jayakumar Rangasamy, N, A. Kumar., and S, M., “Redox-responsive Cystamine Conjugated Chitin-Hyaluronic Acid Composite Nanogels”, RSC Advances, vol. 4, no. 91, 2014.[Abstract]


Nanoscale carriers were developed to overcome the challenging barriers for the targeted intracellular delivery of chemotherapeutic agents, in particular within tumors. We demonstrate redox responsive cystamine (Cys) conjugated hyaluronic acid (HA)–chitin (CNG) nanogels for the intracellular delivery of doxorubicin (DOX) within colon cancer cells. Chitin, having a slow degrading property, could make HA to slowly degrade, thus protecting the DOX from a sudden burst release, and HA, being a ligand for the CD44 receptor, are over expressed in colon cancer cells (HT-29). 150–200 nm sized DOX-HA-CNGs and DOX-HA-Cys-CNGs were developed and characterized by DLS, Zeta, TG/DTA, FT-IR, EDAX and rheological techniques. The composite nanogel preparations proved to be safe for intravenous administration because they were non-hemolytic and did not interfere with the coagulation cascade. Flow cytometric and fluorescent microscopic analysis proved the specific internalization of DOX-HA-CNGs within HT-29 cells (CD-44 +ve). MTT assay revealed the superior anti-proliferative activity of DOX-HA-Cys-CNGs in CD-44 +ve HT-29 cells compared to that in CD-44 −ve IEC-6 cells. Thus, HA-Cys-CNGs are proven to be a better carrier for the selective, redox responsive and intracellular delivery of DOX.

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2014

Journal Article

S. Deepthi, Viha, C. V. Sidhy, Thitirat, C., Furuike, T., Tamura, H., and Dr. Jayakumar Rangasamy, “Fabrication of Chitin/Poly(butylene succinate)/Chondroitin Sulfate Nanoparticles Ternary Composite Hydrogel Scaffold for Skin Tissue Engineering”, Polymers, vol. 6, pp. 2974–2984, 2014.[Abstract]


Skin loss is one of the oldest and still not totally resolved problems in the medical field. Since spontaneous healing of the dermal defects would not occur, the regeneration of full thickness of skin requires skin substitutes. Tissue engineering constructs would provide a three dimensional matrix for the reconstruction of skin tissue and the repair of damage. The aim of the present work is to develop a chitin based scaffold, by blending it with poly(butylene succinate) (PBS), an aliphatic, biodegradable and biocompatible synthetic polymer with excellent mechanical properties. The presence of chondroitin sulfate nanoparticles (CSnp) in the scaffold would favor cell adhesion. A chitin/PBS/CSnp composite hydrogel scaffold was developed and characterized by SEM (Scanning Electron Microscope), FTIR (Fourier Transform Infrared Spectroscopy), and swelling ratio of scaffolds were analyzed. The scaffolds were evaluated for the suitability for skin tissue engineering application by cytotoxicity, cell attachment, and cell proliferation studies using human dermal fibroblasts (HDF). The cytotoxicity and cell proliferation studies using HDF confirm the suitability of the scaffold for skin regeneration. In short, these results show promising applicability of the developed chitin/PBS/CSnps ternary composite hydrogel scaffolds for skin tissue regeneration.

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2014

Journal Article

J. - J. Lee, Jeong, K. Jae, Hashimoto, M., Kwon, A. H., Rwei, A., Dr. Sahadev Shankarappa, Tsui, J. H., and Kohane, D. S., “Synthetic Ligand-Coated Magnetic Nanoparticles for Microfluidic Bacterial Separation from Blood”, Nano Letters, vol. 14, pp. 1-5, 2014.[Abstract]


Bacterial sepsis is a serious clinical condition that can lead to multiple organ dysfunction and death despite timely treatment with antibiotics and fluid resuscitation. We have developed an approach to clearing bacteria and endotoxin from the bloodstream, using magnetic nanoparticles (MNPs) modified with bis-Zn-DPA, a synthetic ligand that binds to both Gram-positive and Gram-negative bacteria. Magnetic microfluidic devices were used to remove MNPs bound to Escherichia coli, a Gram-negative bacterium commonly implicated in bacterial sepsis, from bovine whole blood at flows as high as 60 mL/h, resulting in almost 100% clearance. Such devices could be adapted to clear bacteria from septicemic patients.

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2014

Journal Article

Dr. Sahadev Shankarappa, Dr. Manzoor K., and Shantikumar V Nair, “Efficacy versus Toxicity - The Yin and Yang in translating nanomedicines,”, Nanomaterials and Nanotechnology, vol. 4, no. 23, 2014.[Abstract]


Nanomedicine, as a relatively new offshoot of nanotechnology, has presented vast opportunities in biomedical research for developing novel strategies to treat diseases. In the past decade, there has been a significant increase in in vitro and preclinical studies addressing the benefits of nanomedicines. In this commentary, we focus specifically on the efficacy- and toxicity-related translational challenges of nanocarrier-mediated systems, and briefly discuss possible strategies for addressing such issues at in vitro and preclinical stages. We address questions related specifically to the balance between toxicity and efficacy, a balance that is expected to be substantially different for nanomedicines compared to that for a free drug. Using case studies, we propose a ratiometric assessment tool to quantify the overall benefit of nanomedicine as compared to free drugs in terms of efficacy and toxicity. The overall goal of this commentary is to emphasize the strategies that promote the translation of nanomedicines, especially by learning lessons from previous translational failures of other drugs and devices, and to apply these lessons to critically assess data at the basic stages of nanomedicinal research.

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2013

Journal Article

S. Maya, Sarmento, B., Nair, A., Rejinold, N. S., Nair, S. V., and Dr. Jayakumar Rangasamy, “Smart Stimuli Sensitive Nanogels in Cancer Drug Delivery and Imaging: A Review”, Current Pharmaceutical Design, vol. 19, pp. 7203-7218, 2013.[Abstract]


Nanogels are nanosized hydrogel particles formed by physical or chemical cross-linked polymer networks. The advantageous properties of nanogels related to the ability of retaining considerable amount of water, the biocompatibility of the polymers used, the ability to encapsulate and protect a large quantity of payload drugs within the nanogel matrix, the high stability in aqueous media, their stimuli responsively behavior potential, and the versatility in release drugs in a controlled manner make them very attractive for use in the area of drug delivery. The materials used for the preparation of nanogels ranged from natural polymers like ovalbumin, pullulan, hyaluronic acid, methacrylated chondroitin sulfate and chitosan, to synthetic polymers like poly (N-isopropylacrylamide), poly (N-isopropylacrylamide-co-acrylic acid) and poly (ethylene glycol)-b-poly (methacrylic acid). The porous nanogels have been finding application as anti-cancer drug and imaging agent reservoirs. Smart nanogels responding to external stimuli such as temperature, pH etc can be designed for diverse therapeutic and diagnostic applications. The nanogels have also been surface functionalized with specific ligands aiding in targeted drug delivery. This review focus on stimuli-sensitive, multi-responsive, magnetic and targeted nanogels providing a brief insight on the application of nanogels in cancer drug delivery and imaging in detail. © 2013 Bentham Science Publishers.

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2013

Journal Article

A. A. Madhavan, Mohandas, A., Licciulli, A., Sanosh, K. P., Praveen, P., Dr. Jayakumar Rangasamy, Nair, S. V., Nair, A. S., and Balakrishnan, A., “Electrospun continuous nanofibers based on a TiO2-ZnO-graphene composite”, RSC Advances, vol. 3, pp. 25312-25316, 2013.[Abstract]


The present study provides the first reports on the electrospinning of TiO2-ZnO-graphene composite nanofibers for photovoltaic and biomedical applications. These nanofibers were characterized by spectroscopic and microscopic techniques to evaluate the morphologies and phases. The fiber diameter was found to be ∼210 nm. The graphene content was maintained in the range of 0.2-0.7 weight percent. It was observed that when the graphene content was increased beyond 0.7 weight percent, the continuous fiber morphology was lost. Raman spectroscopy was used to confirm the presence of graphene. Conductivity studies showed a ∼9 times increase in conductance values for the TiO2-ZnO-graphene system as compared to TiO2-ZnO nanofibers. Employing these TiO2-ZnO-graphene fiber composites as photoanodes in dye sensitized solar cells, an efficiency of 3.7% was attained. Antibacterial studies performed on two bacterial strains, namely E.coli and S. aureus, have shown that these composite fibers can be used effectively for antibacterial wound dressing applications. This journal is © The Royal Society of Chemistry.

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2013

Journal Article

A. S. Nair, Chacko, D. K., Madhavan, A. A., Arun, T. A., S. Thomas, Anjusree, G. S., Deepak, T. G., Balakrishnan, A., Subramanian, K. R. V., Sivakumar, N., and Nair, S. V., “Ultrafine TiO2 nanofibers for photocatalysis”, RSC Advances, vol. 3, pp. 24858-24862, 2013.[Abstract]


We report a simple synthesis route for producing ultrafine porous TiO 2 nanofibers (∼10 nm diameters) from electrospun rice-shaped TiO2 nanostructures. The rice-shaped TiO2 obtained by annealing the as-spun TiO2-PVAc composite nanofibers was treated with concentrated alkali (with KOH under hydrothermal conditions) followed by acid treatment and low temperature sintering. The alkali treatment produces the titanate (K2Ti3O7) which undergoes exchange of ions (protons) during the acid treatment resulting in H2Ti 3O7. The heat treatment of the protonated titanate (H 2Ti3O7) results in their conversion to ultrafine TiO2 (titanate-derived TiO2) nanofibers. The rice-shaped TiO2 and the titanate-derived TiO2 nanofibers were characterized by SEM, TEM, XRD, XPS, Raman and BET measurements and the latter has ∼2.5 times higher surface area than the former. The TiO 2 nanofibers showed superior photocatalytic applications than the commercial P-25 TiO2. This journal is © The Royal Society of Chemistry.

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2013

Journal Article

G. L. Malarvizhi, Chandran, P., Retnakumari, A. P., Ramachandran, R., Gupta, N., Nair, S., and Koyakutty, M., “A rationally designed photo-chemo core-shell nanomedicine for inhibiting the migration of metastatic breast cancer cells followed by photodynamic killing”, Nanomedicine: Nanotechnology, Biology, and Medicine, 2013.[Abstract]


<p>A multifunctional core-shell nanomedicine capable of inhibiting the migratory capacity of metastatic cancer cells followed by imparting cytotoxic stress by photodynamic action is reported. Based on in silico design, we have developed a core-shell nanomedicine comprising of &nbsp; 80 nm size poly(lactic-co-glycolic acid) (PLGA) nano-core encapsulating photosensitizer, m-tetra(hydroxyphenyl)chlorin (mTHPC), and &nbsp; 20 nm size albumin nano-shell encapsulating tyrosine kinase inhibitor, Dasatinib, which impair cancer migration. This system was prepared by a sequential process involving electrospray of polymer core and coacervation of protein shell. Cell studies using metastatic breast cancer cells demonstrated disruption of Src kinase involved in the cancer migration by albumin-dasatinib nano-shell and generation of photoactivated oxidative stress by mTHPC-PLGA nano-core. This unique combinatorial photo-chemo nanotherapy resulted synergistic cytotoxicity in &nbsp; 99% of the motility-impaired metastatic cells. This approach of blocking cancer migration followed by photodynamic killing using rationally designed nanomedicine is a promising new strategy against cancer metastasis. © 2013.</p>

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2013

Journal Article

J. C. Mohan, Praveen, G., Chennazhi, K. P., Jayakumar, R., and Shantikumar V Nair, “Functionalised Gold Nanoparticles for Selective Induction of in Vitro Apoptosis among Human Cancer Cell Lines”, Journal of Experimental Nanoscience, vol. 8, pp. 32-45, 2013.[Abstract]


The interaction of citrate- and polyethylene imine (PEI)-functionalised gold nanoparticles (GNP) with cancer cell lines with respect to the cellular response was studied. It was found that GNP/citrate nanoparticles were able to induce apoptosis in human carcinoma lung cell lines A549, but GNP/PEI did not show any reduction in the viability of the cells in human breast cancer cell line MCF-7 and A549 cell lines. FACS data confirmed that the number of apoptotic cells increased with increase in the concentration of GNP/citrate nanoparticles. Decline in cellular expansion and changes in the nuclear morphology were noted after the treatment of GNP/citrate nanoparticles on A549 cell lines, which itself is a direct response for stress induction. The induction of cellular apoptosis was further confirmed by DNA fragmentation assay. These data confirm the potential of GNP/citrate nanoparticle to evoke cell-specific death response in the A549 cell lines. © 2013 Taylor & Francis.

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2013

Journal Article

N. S. Binulal, Natarajan, A., Dr. Deepthy Menon, Bhaskaran, V. K., Dr. Ullas Mony, and Shantikumar V Nair, “PCL-gelatin composite nanofibers electrospun using diluted acetic acid-ethyl acetate solvent system for stem cell-based bone tissue engineering”, Journal of Biomaterials Science, Polymer Edition, vol. 25, no. 4, 2013.[Abstract]


Composite nanofibrous scaffolds with various poly(ε-caprolactone) (PCL)/gelatin ratios (90:10, 80:20, 70:30, 60:40, 50:50 wt.%) were successfully electrospun using diluted acetic and ethyl acetate mixture. The effects of this solvent system on the solution properties of the composites and its electrospinning properties were investigated. Viscosity and conductivity of the solutions, with the addition of gelatin, allowed for the electrospinning of uniform nanofibers with increasing hydrophilicity and degradation. Composite nanofibers containing 30 and 40 wt.% gelatin showed an optimum combination of hydrophilicity and degradability and also maintained the structural integrity of the scaffold. Human mesenchymal stem cells (hMSCs) showed favorable interaction with and proliferation on, the composite scaffolds. hMSC proliferation was highest in the 30 and 40 wt.% gelatin containing composites. Our experimental data suggested that PCL-gelatin composite nanofibers containing 30-40 wt.% of gelatin and electrospun in diluted acetic acid-ethyl acetate mixture produced nanofiber scaffolds with optimum hydrophilicity, degradability, and bio-functionality for stem cell-based bone tissue engineering.

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2013

Journal Article

M. Vab Reddy, Jie, T. Wac, Jafta, C. Jd, Ozoemena, K. Ide, Mathe, M. Kd, Nair, A. Sf, Peng, S. Sg, Idris, M. Sg, Balakrishna, Gh, Ezema, F. Ii, and Chowdari, B. V. Ra, “Studies on Bare and Mg-doped LiCoO2 as a cathode material for Lithium ion Batteries”, Electrochimica Acta, 2013.[Abstract]


In this paper, we report on the preparation of bare and Mg-doped Li(MgxCo1-x)O2 (x = 0, 0.03, 0.05) phases by a molten salt method and their electrochemical properties. They were prepared at 800 °C for 6 h in air. Rietveld refined X-Ray Diffraction data of bare (x = 0) and Mg-doped (x = 0.03, 0.05) compounds show a well-ordered hexagonal layer-type structure (a ∼ 2.81 Å, c ∼ 14.05 Å). Scanning Electron Microscopy (SEM) show hexagonal type morphology at 800 °C. Powder density was close to 5.02 gcm-3, which compares well with the theoretical value. Electrochemical properties were studied in the voltage range of 2.5-4.3 V vs. Li using Cyclic Voltammetry (CV) and galvanostatic cycling. CV studies on bare and Mg-doped LiCoO2 show main cathodic and anodic redox peaks at ∼ 3.9 V and ∼ 4.0 V, respectively. Galvanostatic cycling of Li(MgxCo1-x)O2 (x = 0, 0.03, 0.05) showed reversible capacity values at the 60th cycle to be: 147 (±3) mAh g-1 (x = 0), 127 (±3) mAh g-1 (x = 0.03), and 131 (±3) mAh g-1 (x = 0.05) cycled at a current density of 30 mA g-1. Capacity retention is also favourable at 98.5%. Crown Copyright © 2013.

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2013

Journal Article

K. T. Shalumon, Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “High Thick Layer-by-Layer 3D Multiscale Fibrous Scaffolds for Enhanced Cell Infiltration and It's Potential in Tissue Engineering”, Journal of Biomedical Nanotechnology, vol. 9, pp. 2117-2122, 2013.[Abstract]


This work explains the fabrication and potential applicability of high thick three dimensional (3-D) electrospun multiscale fibrous scaffolds in tissue engineering by focusing on the possible fabrication techniques. Multiscale fibrous scaffold of poly(lactic acid) (PLA) was fabricated by combining nano and micro fibers in optimum concentrations. Finely chopped multiscale fibers were allowed to undergo compression, freeze-drying, resin embedding, cryo-grinding and layering techniques to make 3D scaffolds and the layer-by-layer method was found to be most suitable for 3-D scaffold fabrication. Cell studies in layered 3D scaffolds were performed using MG 63 cells and infiltration was observed using SEM and confocal microscope. Since the layered high thick 3D scaffold perfectly complies with the requirements, this could be proposed as one of the suitable methods for constructing 3D scaffolds for tissue engineering applications

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2013

Journal Article

P. Praveen, Ravi, S., Soumya, M. S., Binitha, G., Balakrishnan, A., Subramanian, K. R. V., Nair, V. S., and Sivakumar, N., “Thin film electrodes derived from nano structured carbon coated LiFePO4 composite for rechargeable lithium ion batteries”, Science of Advanced Materials, vol. 5, pp. 2021-2026, 2013.[Abstract]


The present study provides the detailed experimental reports on the electrophoretic co-deposition of camphor derived carbon coated onto LiFePO4 nano particles which has been used for fabricating high surface area rechargeable cathodes. X-ray diffraction analysis revealed the single crystals of the orthorhombic olivine structure of LiFePO4 and transmission electron microscopy image indicated homogeneous carbon coating over LiFePO4. The presence of sp2 hybridized carbon on LiFePO4 particles and oxidation states of iron were confirmed using X-ray photoelectron spectroscopy. Electrochemical characterizations were performed using cyclic voltammetry and electrochemical impedance spectroscopy. The specific capacity was found to be 100±5 mA h g-1 for the pristine sample, whereas it is enhanced to 140±3 mA h g-1 for LiFePO4-C composite. The carbon coated LiFePO4 showed 96% retention in capacity as compared to pristine LiFePO4 (53%). The result indicated that the specific capacity and electronic conductivity of LiFePO4 have been improved by proper carbon coating. © 2013 by American Scientific Publishers.

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2013

Journal Article

C. C. Mohan, Chennazhi, K. P., and Menon, D., “In vitro hemocompatibility and vascular endothelial cell functionality on titania nanostructures under static and dynamic conditions for improved coronary stenting applications”, Acta Biomaterialia, vol. 9, pp. 9568-9577, 2013.[Abstract]


The usefulness of nanoscale topography in improving vascular response in vitro was established previously on hydrothermally modified titanium surfaces. To propose this strategy of surface modification for translation onto clinically used metallic stents, it is imperative that the surface should be also hemocompatible: an essential attribute for any blood-contacting device. The present in vitro study focuses on a detailed hemocompatibility evaluation of titania nanostructures created through an alkaline hydrothermal route on metallic Ti stent prototypes. Direct interactions of TiO2 nanocues of various morphologies with whole blood were studied under static conditions as well as using an in vitro circulation model mimicking arterial flow, with respect to a polished Ti control. Nanomodified stent surfaces upon contact with human blood showed negligible hemolysis under constant shear and static conditions. Coagulation profile testing indicated that surface roughness of nanomodified stents induced no alterations in the normal clotting times, with insignificant thrombus formation and minimal inflammatory reaction. Endothelialized nanomodified Ti surfaces were found to inhibit both activation as well as aggregation of platelets compared with the control surface, with the endothelium formed on the nanosurfaces having an increased expression of anti-thrombogenic genes. Such a nanotextured Ti surface, which is anti-thrombogenic and promotes endothelialization, would be a cost-effective alternative to drug-eluting stents or polymer-coated stents for overcoming in-stent restenosis. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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2013

Journal Article

T. S. Sonia, Sivakumar, N., Balakrishnan, A., Nair, S., Subramanian, K. R. V., and Shantikumar V Nair, “Thin Film Carbon-sulfur Cathodes by Electrophoretic Deposition for a Prototype Lithium Sulfur Battery System”, Science of Advanced Materials, vol. 5, pp. 1828-1836, 2013.[Abstract]


The present study reports on the fabrication of thin-film nanocomposites of activated carbon-sulfur prepared by electrophoretic deposition onto titanium plates, as cathode materials for a prototype battery. A key aspect of this study is the deposition process, which provides a uniform and fine highly porous microstructure for the cathode. The electrophoretic process is simple, less energy intensive with more control of the C-S ratios and particle sizes than some of the reported methods. The study investigates the performance of this cathode material against a pre-lithiated silicon anode as well as against conventional Li foil anodes. With the conventional Li anodes the results (an energy density of about 690±10 W h kg-1) are comparable to those currently in the literature for full cells. With pre-lithiated Si anodes, the electrophoretic architecture gives improved voltages and improved cycling stability compared to other studies where complex C-S architectures are used, and this appears to be related in part to lower S dissolution in these deposited structures. Overall, the results indicated the strength of the simple electrophoretic process for preparation of the carbon-sulfur cathode material. © 2013 by American Scientific Publishers.

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2013

Journal Article

Pa Chandran, Kavalakatt, Aa, Malarvizhi, G. La, Vasanthakumari, D. R. V. Na, Retnakumari, A. Pa, Sidharthan, Nb, Pavithran, Kb, Nair, Sa, and Dr. Manzoor K., “Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases”, Nanomedicine: Nanotechnology, Biology, and Medicine, 2013.[Abstract]


Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n = 9), including refractory and relapsed cases, and three representative cell lines expressing CD34+/CD38- stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having   100 nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. © 2013 Elsevier Inc. All rights reserved.

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2013

Journal Article

D. Narayanan, Anitha, A., Dr. Jayakumar Rangasamy, and Chennazhi, K. P., “In vitro and in vivo evaluation of osteoporosis therapeutic peptide PTH 1-34 loaded PEGylated chitosan nanoparticles”, Molecular Pharmaceutics, vol. 10, pp. 4159-4167, 2013.[Abstract]


Oral formulation of human parathyroid hormone 1-34 (PTH 1-34) is an alternative patient compliant route in treating osteoporosis. PTH 1-34 loaded chitosan nanoparticles were PEGylated (PEG-CS-PTH NPs) and characterized by DLS, SEM, TEM and FTIR. PEG-CS-PTH NP aggregates of 200-250 nm which in turn comprised 20 nm individual nanoparticles were observed in SEM and TEM images respectively. The PEG-CS-PTH NP with 40% encapsulation efficiency was subjected to an in vitro release in simulated rat body fluids. PEG-CS-PTH NP treated human primary osteoblast cells, upon PTH 1-34 receptor activation, produced second messenger-cAMP, which downstream stimulated intracellular calcium uptake, production of bone specific alkaline phosphatase, osteocalcin etc., which substantiates the anabolic effect of the peptide. PEG-CS-PTH NPs showed an oral bioavailability of 100-160 pg/mL PTH 1-34 throughout 48 h, which is remarkable compared to the bare PTH 1-34 and CS-PTH NPs. The NIR image of gastrointestinal transit of ICG conjugated PEG-CS-PTH NPs supports this significant finding. © 2013 American Chemical Society.

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2013

Journal Article

P. Chandran, Gupta, N., Retnakumari, A. P., Malarvizhi, G. L., Keechilat, P., Nair, S., and Dr. Manzoor K., “Simultaneous Inhibition of Aberrant Cancer Kinome Using Rationally Designed Polymer-Protein Core-shell Nanomedicine”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 9, pp. 1317-1327, 2013.[Abstract]


Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34+/CD38-) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core ( 250nm) loaded with mTOR inhibitor, everolimus, and albumin shell ( 25nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure ( 290nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. From the Clinical Editor: These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use. © 2013 Elsevier Inc.

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2013

Journal Article

A. K. Varma, “Charcot Neuroarthropathy of the Foot and Ankle: A Review”, Journal of Foot and Ankle Surgery, vol. 52, pp. 740-749, 2013.[Abstract]


Charcot neuroarthropathy is a limb-threatening, destructive process that occurs in patients with neuropathy associated with medical diseases such as diabetes mellitus. Clinicians' treating diabetic patients should be vigilant in recognizing the early signs of acute Charcot neuroarthropathy, such as pain, warmth, edema, or pathologic fracture in a neuropathic foot. Early detection and prompt treatment can prevent joint and bone destruction, which, if untreated, can lead to morbidity and high-level amputation. A high degree of suspicion is necessary. Once the early signs have been detected, prompt immobilization and offloading are important. Treatment should be determined on an individual basis, and it must be determined whether a patient can be treated conservatively or will require surgical intervention when entering the chronic phase. If diagnosed early, medical and conservative measures only will be required. Surgery is indicated for patients with severeor unstable deformities that, if untreated, will result in major amputations. A team approach that includes a foot and ankle surgeon, a diabetologist, a physiotherapist, a medical social councilor, and, most importantly, the patient and immediate family members is vital for successful management of this serious condition. © 2013 American College of Foot and Ankle Surgeons.

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2013

Journal Article

B. S. Anisha, Dr. Raja Biswas, Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds”, International Journal of Biological Macromolecules, vol. 62, pp. 310-320, 2013.[Abstract]


The aim of this work was to develop an antimicrobial sponge composed of chitosan, hyaluronic acid (HA) and nano silver (nAg) as a wound dressing for diabetic foot ulcers (DFU) infected with drug resistant bacteria. nAg (5-20. nm) was prepared and characterized. The nanocomposite sponges were prepared by homogenous mixing of chitosan, HA and nAg followed by freeze drying to obtain a flexible and porous structure. The prepared sponges were characterized using SEM and FT-IR. The porosity, swelling, biodegradation and haemostatic potential of the sponges were also studied. Antibacterial activity of the prepared sponges was analysed using Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Klebsiella pneumonia. Chitosan-HA/nAg composite sponges showed potent antimicrobial property against the tested organisms. Sponges containing higher nAg (0.005%, 0.01% and 0.02%) concentrations showed antibacterial activity against MRSA. Cytotoxicity and cell attachment studies were done using human dermal fibroblast cells. The nanocomposite sponges showed a nAg concentration dependent toxicity towards fibroblast cells. Our results suggest that this nanocomposite sponges could be used as a potential material for wound dressing for DFU infected with antibiotic resistant bacteria if the optimal concentration of nAg exhibiting antibacterial action with least toxicity towards mammalian cells is identified. © 2013 Elsevier B.V.

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2013

Journal Article

K. M. Sajesh, Dr. Jayakumar Rangasamy, Nair, S. V., and Chennazhi, K. P., “Biocompatible Conducting Chitosan/polypyrrole-alginate Composite Scaffold for Bone Tissue Engineering”, International Journal of Biological Macromolecules, vol. 62, pp. 465-471, 2013.[Abstract]


A polypyrrole based conducting scaffold was developed by incorporating polypyrrole-alginate (PPy-Alg) blend with chitosan using lyophilization technique and employed this composite as a substrate for bone tissue engineering. PPy-Alg blend was developed by oxidative chemical synthesis of polypyrrole using FeCl3 as oxidizing agent and characterized. The physiochemical characterization of the scaffold was done using SEM, FT-IR along with porosity measurement, swelling and in vitro degradation studies. Surface conductivity of the scaffolds was analyzed using Scanning Electrochemical microscopy (SECM). Results from cell viability and cell proliferation with MG-63 cells using Alamar blue assay confirmed the cytocompatible nature of the developed scaffold. In vitro biomineralization ability of the scaffold was assessed and thus the effectiveness of PPy-Alg/chitosan scaffold in the field of tissue engineering was evaluated. © 2013 Elsevier B.V.

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2013

Journal Article

T. R. Arunraj, N. Rejinold, S., N. Kumar, A., and Dr. Jayakumar Rangasamy, “Doxorubicin-chitin-poly(caprolactone) composite nanogel for drug delivery”, International Journal of Biological Macromolecules, vol. 62, pp. 35-43, 2013.[Abstract]


In this work, we developed a pH responsive chitin-poly(caprolactone) composite nanogels (chitin-PCL CNGs) system for non-small cell lung cancer (NSCLC). A hydrophilic drug, doxorubicin (Dox) was loaded in Chitin-PCL CNGs (Dox-chitin-PCL CNGs). Both control and drug loaded systems were analyzed by DLS, SEM, FTIR and TG/DTA. The size ranges of the control composite nanogels and their drug loaded counterparts were found to be 70. ±. 20 and 240. ±. 20. nm, respectively. The control chitin-PCL CNGs and Dox-chitin-PCL CNGs showed higher swelling and degradation in acidic pH. Drug entrapment efficiency and in-vitro drug release studies were carried out and showed a higher drug release at acidic pH compared to neutral pH. Cellular internalization of the nanogel systems was confirmed by fluorescent microscopy. Dox-Chitin-PCL CNGs showed dose dependent cytotoxicity toward A549 (adenocarcinomic human alveolar basal epithelial cells) cancer cells. Furthermore, the results of in-vitro hemolytic assay and coagulation assay substantiate the blood compatibility of the system. These results indicate that chitin-PCL CNGs is a novel carrier for delivery of anticancer drugs. © 2013 Elsevier B.V.

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2013

Journal Article

A. Sasidharan, Girish C. M., Gowd, G. S., Nair, S., and Dr. Manzoor K., “Confocal Raman Imaging Study Showing Macrophage Mediated Biodegradation of Graphene in Vivo”, Advanced Healthcare Materials, vol. 2, pp. 1489-1500, 2013.[Abstract]


This study is focused on the crucial issue of biodegradability of graphene under in vivo conditions. Characteristic Raman signatures of graphene are used to three dimensionally (3D) image its localization in lung, liver, kidney and spleen of mouse and identified gradual development of structural disorder, happening over a period of 3 months, as indicated by the formation of defect-related D'band, line broadening of D and G bands, increase in ID/IG ratio and overall intensity reduction. Prior to injection, the carboxyl functionalized graphene of lateral size ∼200 nm is well dispersed in aqueous medium, but 24 hours post injection, larger aggregates of size up to 10 μm are detected in various organs. Using Raman cluster imaging method, temporal development of disorder is detected from day 8 onwards, which begins from the edges and grows inwards over a period of 3 months. The biodegradation is found prominent in graphene phagocytosed by tissue-bound macrophages and the gene expression studies of pro-inflammatory cytokines indicated the possibility of phagocytic immune response. In addition, in vitro studies conducted on macrophage cell lines also show development of structural disorder in the engulfed graphene, reiterating the role of macrophages in biodegradation. This is the first report providing clear evidence of in vivo biodegradation of graphene and these results may radically change the perspective on potential biomedical applications of graphene. © 2013 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.

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2013

Journal Article

A. N. Kumar, N. Rejinold, S., Anjali, P., Balakrishnan, A., Dr. Raja Biswas, and Dr. Jayakumar Rangasamy, “Preparation of chitin nanogels containing nickel nanoparticles”, Carbohydrate Polymers, vol. 97, pp. 469-474, 2013.[Abstract]


In this work, we developed 120-150 nm sized nickel nanoparticles loaded chitin nanogels (Ni-Chitin NGs) by regeneration chemistry approach to investigate and determine its cytocompatibility and antibacterial activity against Staphylococcus aureus. The nickel nanoparticles were prepared by hydrothermal method. The prepared Ni-Chitin NGs were well characterized by SEM, FTIR, TG/DTA/DTG and XRD and the in vitro cytocompatibility was tested on A549 and L929 cells which showed that they are completely non-toxic. Ni-Chitin NGs showed better toxicity to the bacterial strains when compared to previous study with other nanoparticles using serial dilution method. The rhodamine labeled-Ni-Chitin NGs showed cellular localization on both L929 and A549 cells without perturbing their cellular constituents. These studies showed that the Ni-Chitin NGs could be used for various applications in biomedical filed. © 2013 Elsevier Ltd. All rights reserved. More »»

2013

Journal Article

G. Binitha, Soumya, M. S., Madhavan, A. A., Praveen, P., Balakrishnan, A., Subramanian, K. R. V., Reddy, M. V., Nair, S. V., Nair, A. S., and Sivakumar, N., “Electrospun α-Fe2O3 nanostructures for supercapacitor applications”, Journal of Materials Chemistry A, vol. 1, pp. 11698-11704, 2013.[Abstract]


Herein, we report the facile synthesis of two α-Fe2O 3 nanostructures with different morphologies via an electrospinning technique using ferric acetyl acetonate as a precursor and polyvinyl acetate and polyvinyl pyrrolidone as the respective polymers. The as-electrospun metal oxide-polymer composite fibers were sintered at 500 °C to obtain two distinct nanostructures, denoted as nanograins and porous fibers throughout this manuscript. These crystalline nanostructures were characterized using powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDAX) and transmission electron microscopy (TEM). The characterization results elucidated the predominance of hematite (α-Fe2O3) with particle sizes of 21 and 53 nm, for the respective nanostructures. Electrophoretic deposition was carried out in order to fabricate thin film electrodes, which were then subjected to electrochemical analysis. Electrochemical characterization revealed that both of the fabricated electrodes exhibited excellent performance in 1 M LiOH electrolyte with specific capacitance values of 256 and 102 F g-1 for the porous fiber and nanograin structures, respectively, at a scan rate of 1 mV s-1 and excellent capacitance retention, even after 3000 cycles, thus making them promising electrode materials for energy storage devices. © 2013 The Royal Society of Chemistry.

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2013

Journal Article

R. Ranjusha, Ramakrishna, S., Nair, A. S., Anjali, P., Vineeth, S., Sonia, T. S., Sivakumar, N., Subramanian, K. R. V., Nair, S. V., and Balakrishnan, A., “Fabrication and performance evaluation of button cell supercapacitors based on MnO2 nanowire/carbon nanobead electrodes”, RSC Advances, vol. 3, pp. 17492-17499, 2013.[Abstract]


The present study provides in detail experimental results on the synthesis and characterization of carbonized MnO2 nanowires for fabricating large surface area, high power and energy density rechargeable electrodes for supercapacitor/battery applications. High aspect ratio MnO2 nanowires carbonized with camphoric carbon composed of nanobeads were utilized for this purpose. The graphitic nature of these nanobeads was confirmed through Raman spectroscopy and X-ray photoelectron spectroscopy, where a predominance of sp2 hybridization was observed. The relative contributions of the carbon nanobeads' influence on the capacitive and diffusion controlled processes underlying these thin film electrodes have been mathematically modelled. The electrodes were fabricated into thin films (thickness ∼30 μm) by co-electrophoresis onto titanium foils exhibiting a surface area of ∼50 m2 g-1. CHN analyses revealed an electrophoretic co-deposition of carbon nanobeads along with MnO2 nanowires onto the titanium foils. From the electrochemical studies, an intrinsic correlation between overall specific capacitance, electrode internal resistance and its conductivity has been defined and explained in different electrolyte systems. These electrodes exhibited specific mass capacitance values as high as 1200 ± 18 F g-1. High cyclic stability was observed at the end of 10=000 cycles, which was attributed to the low oxide dissolution of ∼0.02 ppm in the electrolyte as measured by inductively coupled plasma atomic emission spectroscopy studies. Further, a working model of a button cell was also studied based on these thin film electrodes, which exhibited a capacitance of ∼1.2 F. These thin film electrodes exhibited an energy density of 96 Wh kg-1 and a peak power density of 32 kW kg-1. © 2013 The Royal Society of Chemistry.

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2013

Journal Article

G. S. Anjusree, Bhupathi, A., Balakrishnan, A., Vadukumpully, S., Subramanian, K. R. V., Sivakumar, N., Ramakrishna, S., Nair, S. V., and Nair, A. S., “Fabricating fiber, rice and leaf-shaped TiO2 by tuning the chemistry between TiO2 and the polymer during electrospinning”, RSC Advances, vol. 3, pp. 16720-16727, 2013.[Abstract]


Electrospinning is a facile technique for the fabrication of nanofibers (one-dimensional, 1D, nanostructures) of metals, metal oxides and polymers on a commercial scale which find applications in the fields of energy (dye-sensitized solar cells, Li-ion batteries, fuel cells, etc.), healthcare, environmental engineering and biotechnology (membranes and filters). While electrospinning polymer solutions results in polymer nanofibers, metal oxide nanofibers (say of TiO2) are made by electrospinning a TiO2 precursor along with a polymer into composite nanofibers and subsequently removing the polymer by a sintering process. However, we have found that the morphology of the electrospun TiO2 depends on the chemical nature of the polymer involved and more precisely the chemical interactions between the polymer and the TiO2 during the sintering process. When the polymer is changed from polyvinyl pyrrolidone (PVP) to polyvinyl acetate (PVAc) to a mixture of PVP and PVAc, the morphology of the TiO2 varies from continuous fibre to rice-shaped to leaf-shaped. The present manuscript explores the chemistry between the TiO2 and the above mentioned polymers which results in the structural anisotropy of the electrospun TiO2. The electrospun metal oxides are useful for energy and environmental applications. © The Royal Society of Chemistry 2013.

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2013

Journal Article

D. Narayanan, Gopikrishna, J., J., D., Menon, D., and Shantikumar V Nair, “Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems: Formulation, Properties, and Toxicological Evaluation”, Advances in Polymer Science, vol. 254, pp. 241-268, 2013.[Abstract]


Enhancing the clinical benefits of pharmaceuticals at reduced doses with negligible side effects has been an ever-challenging goal in drug delivery. This pursuit towards an optimal formulation is hugely supported through the development of nanoparticulate delivery systems, which encapsulate the drug in its active form. Nanocarriers have emerged as successful candidates in pharmaceutics owing to their multifaceted characteristics such as the capability to entrap pharmaceutical ingredients at therapeutic dose, better biodistribution, size-dependent clearance, targetability, and controlled/sustained release of single or multiple payloads at the site of interest. Additionally, the requirement that the chosen carrier be biocompatible and biodegradable necessitates the use of biopolymers in entrapping payloads. Among the biopolymers, a wide variety of natural and synthetic carbohydrates and proteins (including starch, chitosan, chitin, dextran, alginate, albumin, casein, fibrin/fibrinogen, gelatin, collagen, whey protein, etc.) have evolved as useful materials for delivering hydrophobic or hydrophilic drugs through oral, intravenous, mucosal, ocular, or nasal routes. Targeted-controlled release of pharmaceuticals to diseased sites, environmentally stimulated drug release at desired locations, and many more drug release strategies have been made available by efficient engineering and nanoformulation of carbohydrate and protein biopolymers. This chapter embodies an in-depth discussion of various carbohydrate- and protein-based nanomedicines with respect to the formulation and properties of the nanoconstructs. The manipulation and utilization of these properties for development of better drug delivery devices is described and the toxicological interactions of these nanocarriers with host physiological systems discussed. © 2013 Springer-Verlag Berlin Heidelberg.

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2013

Journal Article

S. Sowmya, Bumgardener, J. D., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Role of Nanostructured Biopolymers and Bioceramics in Enamel, Dentin and Periodontal Tissue Regeneration”, Progress in Polymer Science, vol. 38, pp. 1748-1772, 2013.[Abstract]


Tissue engineering approach focuses on the regeneration of deficient or damaged tissues of the body. Regeneration of dental tissues is considered as a promising therapeutic approach in dental tissue engineering. Engineering the environment for developing tissues comprises of biomaterials, growth factors, stem cells and regulation of physiological conditions in a spatial and temporal manner. To enhance the structural stability and bioactivity of polymers, a wide variety of nanomaterials are being utilized in dental regenerative medicine. Nanostructured biopolymers in the form of scaffolds, hydrogels, nanofibers, dendrimers, films, etc. and nanostructured bioceramics such as hydroxyapatite, bioactive glass ceramic/bioglass, etc. in the form of nanoparticles, nanocrystals, nanorods, paste, etc. are being exploited in the simultaneous regeneration of hard and soft tissues of the human body. In the dental area, these different forms closely mimic the natural constituents and framework of the dental tissues, namely enamel, dentin and periodontium. Overall this review essentially focuses on the role of polymeric and ceramic nanomaterials in the area of dental tissue engineering, highlighting their specific applications in enamel, dentin and periodontal regeneration. © 2013 Elsevier Ltd.

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2013

Journal Article

M. P. Narayanan, Dr. Damodaran Vasudevan, and Krishnakumar N. Menon, “Analysis of Gene Mutations among South Indian Patients with Maple Syrup Urine Disease: Identification of Four Novel Mutations”, Indian Journal of Geo-Marine Sciences, vol. 50, pp. 442-446, 2013.[Abstract]


Maple syrup urine disease (MSUD) is predominantly caused by mutations in the BCKDHA, BCKDHB and DBT genes, which encode for the E1α, E1β and E2 subunits of the branched-chain a-keto acid dehydrogenase complex, respectively. Because disease causing mutations play a major role in the development of the disease, prenatal diagnosis at gestational level may have significance in making decisions by parents. Thus, this study was aimed to screen South Indian MSUD patients for mutations and assess the genotype-phenotype correlation. Thirteen patients diagnosed with MSUD by conventional biochemical screening such as urine analysis by DNPH test, thin layer chromatography for amino acids and blood amino acid quantification by HPLC were selected for mutation analysis. The entire coding regions of the BCKDHA, BCKDHB and DBT genes were analyzed for mutations by PCR-based direct DNA sequencing. BCKDHA and BCKDHB mutations were seen in 43% of the total ten patients, while disease-causing DBT gene mutation was observed only in 14%. Three patients displayed no mutations. Novel mutations were c.130C&gt;T in BCKDHA gene, c. 599C&gt;T and c.121_122delAC in BCKDHB gene and c.190G&gt;A in DBT gene. Notably, patients harbouring these mutations were non-responsive to thiamine supplementation and other treatment regimens and might have a worse prognosis as compared to the patients not having such mutations. Thus, identification of these mutations may have a crucial role in the treatment as well as understanding the molecular mechanisms in MSUD. © 2013 National Institute of Science Communication and Information Resources (NISCAIR). All rights reserved.

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2013

Journal Article

R. Nadesh, Narayanan, D., P.r., S., Vadakumpully, S., Dr. Ullas Mony, Koyakkutty, M., Shantikumar V Nair, and Dr. Deepthy Menon, “Hematotoxicological analysis of surface-modified and -unmodified chitosan nanoparticles”, Journal of Biomedical Materials Research - Part A, vol. 101, pp. 2957-2966, 2013.[Abstract]


The increasing interest in using chitosan nanoparticles for controlled drug delivery is hampered by its blood incompatibility, especially for intravenous applications. This study investigated the effects of processing solvents (acetic acid/lactic acid), dispersing media (acidic medium/saline), and surface modifiers (polyethylene glycol, polyvinyl alcohol, and ethylenediaminetetraacetatic acid) on the hemocompatibility of chitosan. Blood compatibility of chitosan nanoparticles prepared by ionotropic gelation with altered surface chemistry was evaluated by assessing their hemolytic activity, platelet aggregation, coagulation, and cytokine induction. It was observed that nanoparticles prepared in lactic acid and dispersed in saline did not show hemolysis, platelet aggregation, or coagulation, whereas nanoparticles prepared in acetic acid showed strong hemolysis. Surface modifiers were not observed to significantly affect blood compatibility, with the exception of EDTA, which delayed blood clotting times. Thus, chitosan nanoparticles prepared in lactic acid and dispersed in saline may be an ideal nanocarrier for parenteral applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:2957-2966, 2013. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

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2013

Journal Article

A. Paravannoor, Nair, A. S., Ranjusha, R., Praveen, P., Subramanian, K. R. V., Sivakumar, N., Nair, S. V., and Balakrishnan, A., “Camphoric carbon-grafted Ni/NiO nanowire electrodes for high-performance energy-storage systems”, ChemPlusChem, vol. 78, pp. 1258-1265, 2013.[Abstract]


The present study provides the first report on the preparation and utilization of camphoric carbon nanobeads grafted onto Ni/NiO nanowires for rechargeable electrodes for energy-storage applications. These functionally graded nanowires were electrophoretically deposited onto nickel foils and processed into high-surface-area electrodes. A detailed study has been performed to elucidate the effect of carbon content, different electrolytes, and their concentrations on these nanowires. BET surface area analysis revealed that these grafted nanowires could exhibit a high surface area of about 106a m2 g-1, compared with pristine nanowires, which exhibited a surface area of about 45a m2 g-1. From the analysis of relevant electrochemical parameters, an intrinsic correlation between the capacitance, internal resistance, and the surface morphology has been deduced. Relative contributions of capacitive and diffusion-controlled processes underlying these thin-film electrodes have been mathematically modeled. These thin-film electrodes exhibited specific mass capacitance values as high as (1950±80) and (1140±60)a F g-1, as determined from cyclic voltammetry and charge discharge curves, respectively; t Copyright © 2013 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.

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2013

Journal Article

Anusha Ashokan, Gowd, G. S., Somasundaram, V. H., Bhupathi, A., Peethambaran, R., Unni, A. K. K., ,, Shantikumar V Nair, and Dr. Manzoor K., “Multifunctional Calcium Phosphate Nano-contrast agent for Combined Nuclear, Magnetic and Near-Infrared Invivo Imaging”, Biomaterials, vol. 34, pp. 7143-7157, 2013.[Abstract]


Combination of three imaging techniques such as nuclear, magnetic and near-infrared fluorescence can aid in improved diagnosis of disease by synergizing specific advantages of each of these techniques such as deep tissue penetration of radiation signals, anatomical and functional details provided by magnetic contrast and better spatial resolution of optical signals. In the present work, we report the development of a multimodal contrast agent based on calcium phosphate nanoparticles (nCP), doped with both indocyanine green (ICG) and Gadolinium (Gd3+), and labeled with 99m-Technetium-methylene diphosphonate (99mTc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd3+ and 99mTc were optimized at  0.15wt%, 3.38at% and  0.002ng/mg of nCP, respectively. The leaching-out of ICG was protected by an additional coating of polyethyleneimine (PEI). Toxicological evaluation of the final construct carried out on healthy human mononuclear cells, red-blood cells and platelets, showed excellent hemocompatibility. Invivo multimodal imaging using mice models revealed the ability to provide near-infrared, magnetic and nuclear contrast simultaneously. The nanoparticles also showed the potential for improved MR based angio-imaging of liver. Retention of intravenously administrated nanoparticles in the liver was reduced with PEGylation and the clearance was observed within 48h without causing any major histological changes in vital organs. Thus, we developed a non-toxic tri-modal nano-contrast agent using calcium phosphate nanoparticles and demonstrated its potential for combined nuclear, magnetic and near-infrared imaging invivo. © 2013 Elsevier Ltd.

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2013

Journal Article

S. Srinivasan, Kumar, P. T. Sudheesh, Nair, S. V., Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Antibacterial and bioactive α- And β-chitin hydrogel/ nanobioactive glass ceramic/nano silver composite scaffolds for periodontal regeneration”, Journal of Biomedical Nanotechnology, vol. 9, pp. 1803-1816, 2013.[Abstract]


Alveolar bone loss and bone defects are the commonly encountered periodontal problems. Large defects do not heal spontaneously and thus require surgical interventions with bone substitutes. Bone grafts have the disadvantages of eliciting an immunologic response with subsequent graft rejection. The success rate of Guided Tissue Regeneration (GTR) is variable because of high susceptibility to infection. Thus emerged the important role of synthetic biomaterials and hence for this purpose we developed a nanocomposite scaffold, using α- and β-chitin hydrogel with bioactive glass ceramic nanoparticles (nBGC) and silver nanoparticles (nAg) by lyophilization technique (α- and β-chitin hydrogel/nBGC/nAg nanocomposite scaffold). The prepared nanoparticles and nanocomposite scaffolds were characterized. In addition, the porosity, swelling, mechanical properties, antibacterial activity, in vitro degradation and biomineralization, cell viability, cell attachment and cell proliferation ability of the prepared composite scaffolds were also evaluated. The results showed that α- and β-chitin/nBGC/nAg composite scaffolds were porous and have the capacity to absorb fluids and swell. The composite scaffolds also showed enhanced antibacterial activity, bioactivity and controlled degradation in comparison to the control scaffolds. Cell viability studies proved the non-toxic nature of the nanocomposite scaffolds. Cell attachment and cell proliferation studies revealed the attachment and spreading nature of cells. All these studies revealed that, these antibacterial nanocomposite scaffolds could be a promising approach for the management of periodontal defects. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

P. R. Chandran, Vysakhi, M. V., Manju, S., Kannan, M., S. Kader, A., and A. Nair, S., “In vitro free radical scavenging activity of aqueous and methanolic leaf extracts of Aegle tamilnadensis Abdul Kader (Rutaceae)”, International Journal of Pharmacy and Pharmaceutical Sciences, vol. 5, pp. 819-823, 2013.[Abstract]


Objective: The present study was aimed to find out antioxidant property of methanolic and aqueous extracts of Aegle tamilnadensis Abdul Kader (Rutaceae) leaf. Methods: The phenolic and flavanoid contents of methanolic and aqueous extract were determined. The antioxidant potential of the leaf samples was evaluated by using five in vitro assays such as 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical, superoxide radical, reducing power and metal ion chelating assays. Results: The phenol and flavanoid contents were found to present in considerable quantities. The methanolic leaf extract showed better ability to scavenge superoxide radical (IC50 value of 50.50±0.84μg /ml) followed by hydroxyl radical (IC50 value of 232.95±1.10μg/ml). It also showed good reducing power ability. In contrast, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals were effectively scavenged by aqueous leaf extract (IC50 value of 82.05±1.02 μg/ml). Both the methanolic and aqueous leaf extracts of A. tamilnadensis leaves at 1000 μg/ml showed maximum scavenging activity (91.01% and 95.67%) in quenching metal ions. Conclusions: The results obtained from the present study indicated that the A. tamilnadensis leaf extract is a potent source of natural antioxidants and both the aqueous and methanolic leaf extracts possessed antioxidant property. However methanolic leaf extract showed better antioxidant activity than the aqueous leaf extract.

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2013

Journal Article

Va Sukhithasri, Nisha, Na, Dr. Lalitha Biswas, Kumar, VbAnil, and Dr. Raja Biswas, “Innate immune recognition of microbial cell wall components and microbial strategies to evade such recognitions”, Microbiological Research, vol. 168, pp. 396-406, 2013.[Abstract]


The innate immune system constitutes the first line of defence against invading microbes. The basis of this defence resides in the recognition of defined structural motifs of the microbes called "Microbial associated molecular patterns" that are absent in the host. Cell wall, the outer layer of both bacterial and fungal cells, a unique structure that is absent in the host and is recognized by the germ line encoded host receptors. Nucleotide oligomerization domain proteins, peptidoglycan recognition proteins and C-type lectins are host receptors that are involved in the recognition of bacterial cell wall (usually called peptidoglycan), whereas fungal cell wall components (N- and O-linked mannans, β-glucans etc.) are recognized by host receptors like C-type lectins (Dectin-1, Dectin-2, mannose receptor, DC-SIGN), Toll like receptors-2 and -4 (TLR-2 and TLR-4). These recognitions lead to activation of a variety of host signaling cascades and ultimate production of anti-microbial compounds including phospholipase A2, antimicrobial peptides, lysozyme, reactive oxygen and nitrogen species. These molecules act in cohort against the invading microbes to eradicate infections. Additionally pathogen recognition leads to the production of cytokines, which further activate the adaptive immune system. Both pathogenic and commensal bacteria and fungus use numerous strategies to subvert the host defence. These strategies include bacterial peptidoglycan glycan backbone modifications by O-acetylation, N-deacetylation, N-glycolylation and stem peptide modifications by amidation of meso-Diaminopimelic acid; fungal cell wall modifications by shielding the β-glucan layer with mannoproteins and α-1,3 glucan. This review focuses on the recent advances in understanding the role of bacterial and fungal cell wall in their innate immune recognition and evasion strategies. © 2013 Elsevier GmbH.

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2013

Journal Article

G. S. Anjusree, Nair, A. S., Nair, S. V., and Vadukumpully, S., “One-pot hydrothermal synthesis of TiO2/graphene nanocomposites for enhanced visible light photocatalysis and photovoltaics”, RSC Advances, vol. 3, pp. 12933-12938, 2013.[Abstract]


Two dimensional (2D) nanostructures such as graphene have been attracting increasing research interest in the recent past due to their superior material properties. Herein, we report a facile and scalable method for the production of a few layered graphene sheets and the synthesis of TiO2 nanoparticles on the surface of the prepared graphene sheets using a single step hydrothermal method. The composites prepared with different graphene loading were assessed for their photocatalytic degradation ability under visible light and in dye sensitized solar cells (DSC). The results showed that the average thickness of the obtained graphene sheets was 1.1 nm and the TiO2 nanoparticles were uniformly dispersed on the surface of the graphene. In the photodegradation of methyl orange (MO), the photoactivity of the composite (with 10 wt% graphene loading) was found to be three times better than bare TiO 2 nanoparticles. This increased activity is due to the synergistic effects of TiO2 nanoparticles and graphene sheets. For DSC, composites with 0.7 wt% graphene loading showed a maximum efficiency of 4.26%, 25% higher than without graphene. © The Royal Society of Chemistry 2013.

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2013

Journal Article

Krishnakumar N. Menon, Haridasan, A., Xavier, T., Kundargi, R., and Nair, S., “Neuroproteomics: Are We Biased in Our Representation of Molecular Targets Associated with Specific Domains? Implications in Biomarker Discovery”, Current Proteomics, vol. 10, pp. 56-66, 2013.[Abstract]


The central nervous system (CNS) encompasses complex groups of cells that coexist to form the functional units of brain mainly comprising three cell types: neurons, oligodendrocytes and astrocytes. The network of these cells through interaction between each other leads to formation of complex organizations such as nodes of ranvier, paranodes, juxtaparanodes etc. Therefore, regions of molecular complexity in brain have different protein/lipid combinatorial complexities. Isolation and enrichment of these domains/regions are crucial for the maximum representation of the protein complement,which otherwise goes undetected due to its miniscule amounts in the whole brain homogenate. Thus preparation of enriched fractions representing the proteins of these complexities is important for detection of molecules of pathogenic and diagnostic significance in diseases. Apart from enrichment, the proteins from the enriched fractions have to be solubilized into an appropriate sample format suitable for resolving into its individual protein components. This holds the key to identification of novel molecules important in neurodegenerative diseases. Thus, sample processing for understanding the organizational and functional proteomics becomes an extremely important step for fruitful results to avoid neuroproteomics biases. This review focuses on the functional units of brain, significance of certain molecules in these organizations and how current techniques are meaningfully employed towards neuroproteomics. In addition, we review how custom techniques of sample preparation for protein analysis are being tailored to address issues for a better analysis of protein complement from specialized regions of the functional units of brain in discovering biomarkers pertaining to neurodegenerative diseases. © 2013 Bentham Science Publishers.

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2013

Journal Article

P. Lekha, Balakrishnan, A., Subramanian, K. R. V., and Shantikumar V Nair, “Size Dependent Electron Transfer from CdTe Quantum Dots Linked to TiO 2 Thin Films in Quantum dot Sensitized Solar Cells”, Materials Chemistry and Physics, vol. 141, pp. 216-222, 2013.[Abstract]


{In this present study, we demonstrate the size dependent charge transfer from CdTe quantum dots (QDs) into TiO2 substrate and relate this charge transfer to the actual behavior of a CdTe sensitized solar cell. CdTe QDs was synthesized using mercaptopropionic acid as the capping agent. The conduction band offset for TiO2 and CdTe QDs indicates thermodynamically favorable band edge positions for smaller QDs for the electron-transfer at the QD-TiO2 interface. Time-resolved emission studies were carried out for CdTe QD on glass and CdTe QD on TiO2 substrates. Results on the quenching of QD luminescence, which relates to the transfer kinetics of electrons from the QD to the TiO2 film, showed that at the smaller QD sizes the transfer kinetics are much more rapid than at the larger sizes. I-V characteristics of quantum dot sensitized solar cells (QDSSC) with different sized QDs were also investigated indicating higher current densities at smaller QD sizes consistent with the charge transfer results. The maximum injection rate constant and photocurrent were obtained for 2.5 nm CdTe QDs. We have been able to construct a solar cell with reasonable characteristics (Voc = 0.8 V

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2013

Journal Article

P. A. Mini, Shantikumar V Nair, and Subramanian, K. R. V., “Design and Development of an Integrated Device Consisting of an Independent Solar Cell with Electrical Storage Capacity”, Progress in Photovoltaics: Research and Applications, vol. 21, pp. 1153-1157, 2013.[Abstract]


A thin film-integrated device was constructed consisting of photovoltaic layers combined with additional layers to store charge in real time within the same device. In our design, a dye-sensitized solar cell and capacitor layers are integrated by a double-anodized titanium plate, which consists of TiO 2 nanotubes grown on either side by electrochemical anodization. The combination device can act either as an independent solar cell, a capacitor, or as a solar cell/capacitor device. The results presented here illustrate the capacitive behavior of high surface area nanotubular metal oxide films, with an achieved capacitance of 140 μF cm-2. Copyright © 2012 John Wiley &amp; Sons, Ltd. This study shows the development of an integrated system, which can simultaneously generate and store electricity from a dye-sensitized solar cell. A capacitor is integrated along with the solar cell; this directly charges upon illumination and discharges whenever required. The present study shows a simple and inexpensive method of developing an integrated system, which could replace an independent solar cell and battery system for generation and storage. Copyright © 2012 John Wiley &amp; Sons, Ltd.

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2013

Journal Article

D. Narayanan, Geena, M. G., Lakshmi, H., Nair, S., Menon, D., and Koyakutty, M., “Poly-(ethylene glycol) Modified Gelatin Nanoparticles for Sustained Delivery of the Anti-inflammatory Drug Ibuprofen-Sodium: An in Vitro and in Vivo Analysis”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 9, pp. 818-828, 2013.[Abstract]


The limited bioavailability and rapid clearance of the anti-inflammatory drug Ibuprofen Sodium (IbS) necessitates repeated drug administration. To address this, injectable IbS loaded PEGylated gelatin nanoparticles (PIG NPs) of size  . 200. nm and entrapment efficiency  . 70%, providing sustained release in vitro were prepared by a modified two-step desolvation process. The developed nanomedicine, containing a range of IbS concentrations up to 1. mg/mL proved to be non-toxic, hemocompatible and non-immunogenic, when tested through various in vitro assays and was reaffirmed by in vivo cytokine analysis. HPLC analysis of intravenously administered PIG NPs showed a sustained release of IbS for  . 4. days with improved bioavailability and pharmacokinetics when compared to bare IbS and IbS-loaded non-PEGylated GNPs. Histological analysis of liver and kidney revealed tissue integrity as in the control, indicating biocompatibility of PIG NPs. The results demonstrate improved plasma half-life of IbS when encapsulated within nanogelatin, thereby aiding reduction in its frequency of administration. From the Clinical Editor: In this preclinical study, improved plasma half-life of ibuprofen sodium was demonstrated when encapsulated within PEGylated gelatin nanoparticles of  200 nm size, expected to lead to reduced frequency of administration in future clinical applications. © 2013 Elsevier Inc.

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2013

Journal Article

P. Praveen, Jyothsna, U., Prem, N., Ravi, S., Balakrishnan, A., Subramanian, K. R. V., Nair, A. S., Nair, V. S., and Sivakumar, N., “Thin film rechargeable electrodes based on conductive blends of nanostructured olivine LiFePO4 and sucrose derived nanocarbons for lithium ion batteries”, Journal of Nanoscience and Nanotechnology, vol. 13, pp. 5607-5612, 2013.[Abstract]


The present study provides the first reports of a novel approach of electrophoretic co-deposition technique by which titanium foils are coated with LiFePO4-carbon nanocomposites synthesized by sol gel route and processed into high-surface area cathodes for lithium ion batteries. The study elucidates how sucrose additions as carbon source can affect the surface morphology and the redox reaction behaviors underlying these cathodes and thereby enhance the battery performance. The phase and morphological analysis were done using XRD and XPS where the LiFePO4 formed was confirmed to be a high purity orthorhombic system. From the analysis of the relevant electrochemical parameters using cyclic voltammetry and electrochemical impedance spectroscopy, a 20% increment and 90% decrement in capacity and impedance values were observed respectively. The composite electrodes also exhibited a specific capacity of 130 mA h/g. It has been shown that cathodes based on such composite systems can allow significant room for improvement in the cycling performance at the electrode/electrolyte interface. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

K. C. Kavya, Dr. Jayakumar Rangasamy, Nair, S., and Chennazhi, K. P., “Fabrication and Characterization of Chitosan/gelatin/nSiO2 Composite Scaffold for Bone Tissue Engineering”, International Journal of Biological Macromolecules, vol. 59, pp. 255-263, 2013.[Abstract]


A 3D nanocomposite scaffold of chitosan, gelatin and nano-silica was fabricated by lyophilization to test the hypothesis that incorporation of nano-SiO2 could produce a better candidate for bone tissue engineering compared to pure chitosan and chitosan/gelatin scaffolds. The prepared scaffold was characterized using SEM and FTIR. Porosity, density, swelling, degradation, mechanical integrity, biomineralization and protein adsorption studies, favored it in comparison to the conventional chitosan and chitosan/gelatin scaffolds. In vitro cyto-compatablity, cell attachment-proliferation, ALP activity studies performed using MG-63 cells, advocate its remarkable performance. These cumulative results indicate the prepared nanocomposite scaffold as a prospective candidate for bone tissue engineering. © 2013 Elsevier B.V.

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2013

Journal Article

T. S. Sonia, Mini, P. A., Nandhini, R., Sujith, K., ,, Subramanian, K. R. V., and Shantikumar V Nair, “Composite Supercapacitor Electrodes Made of Activated Carbon/PEDOT:PSS and Activated Carbon/doped PEDOT”, Bulletin of Materials Science, vol. 36, pp. 547-551, 2013.[Abstract]


In this paper, we report on the high electrical storage capacity of composite electrodes made from nanoscale activated carbon combined with either poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) or PEDOT doped with multiple dopants such as ammonium persulfate (APS) and dimethyl sulfoxide (DMSO). The composites were fabricated by electropolymerization of the conducting polymers (PEDOT:PSS, doped PEDOT) onto the nanoscale activated carbon backbone, wherein the nanoscale activated carbon was produced by ball-milling followed by chemical and thermal treatments. Activated carbon/PEDOT:PSS yielded capacitance values of 640 F g-1 and 26mF cm-2, while activated carbon/doped PEDOT yielded capacitances of 1183 F g-1 and 42 mF cm-2 at 10 mV s-1. This is more than five times the storage capacity previously reported for activated carbon-PEDOT composites. Further, use of multiple dopants in PEDOT improved the storage performance of the composite electrode well over that of PEDOT:PSS. The composite electrodes were characterized for their electrochemical behaviour, structural and morphological details and electronic conductivity and showed promise as high-performance energy storage systems. © Indian Academy of Sciences.

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2013

Journal Article

G. S. Anjusree, Asha, A. M., Subramanian, K. R. V., Sivakumar, N., Nair, A. S., Nair, S. V., and Balakrishnan, A., “Facile synthesis of ultrafine TiO2 nanowires with large aspect ratio and its photoactivity”, International Journal of Materials Research, vol. 104, pp. 573-577, 2013.[Abstract]


In the present study, ultrafine TiO2 nanowires (-80 nm in diameter) exhibiting large aspect ratio in the order of 103 were synthesized hydrothermally. Phase and morphological analysis of the nanowires was carried out using X-ray dif- fractometry, X-ray photoelectron spectroscopy and scanning electron microscopy. High resolution transmission electron microscopy revealed the wire exhibiting growth in (101). A Tauc plot derived from UV analysis showed the average band gap values for nanowires to be less than for nanoparticles of similar diameter. It was observed that nanowires exhibited a high degree of photoactivity in an eo- sin-based dye system which was found to be 20-30% more than that of nanoparticles. This high photoactivity in nanowires was attributed to the longer charge retention which was observed during lifetime measurements, resulting in easy radical formation and dye degradation. Lifetime measurements on the nanowires showed the recombination time to be 54 ns as compared to 43 ns for nanoparticles.

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2013

Journal Article

K. T. Shalumon, Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Development of Small Diameter Fibrous Vascular Grafts with Outer Wall Multiscale Architecture to Improve Cell Penetration”, Journal of Biomedical Nanotechnology, vol. 9, pp. 1299-1305, 2013.[Abstract]


This work explains about the development of a unique tubular scaffold for vascular tissue engineering. The inner layer/layers was made up of aligned poly (lactic acid) (PLA) nano fibers and outer layers were composed of random multiscale fibers of poly(caprolactone) (PCL)/PLA providing larger pores for Smooth Muscle Cell (SMC) penetration. The fabricated scaffolds were characterized by SEM. Cell attachment and infiltration studies using SMCs on the multiscale fibers were characterized by SEM and confocal microscopy. Blood compatibility of the scaffold was analysed by haemolysis-coagulation assays, platelet activation studies and the effect of material/fiber alignment on the morphological stability of Red Blood Cells (RBCs) were evaluated using SEM. Since this hierarchically designed tubular scaffold closely mimics the morphology of native vessel, this could be a better candidate for vascular tissue engineering.

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2013

Journal Article

B. Swarnalatha, Nair, S. L., ,, Paul-Prasanth, B., Krishnakumar N. Menon, Hebbel, R. P., Somani, A., Nair, S. V., Milbauer, L. C., and Jayakumar, R., “Poly (Lactic Acid)-chitosan-Collagen Composite Nanofibers as Substrates for Blood Outgrowth Endothelial Cells”, International Journal of Biological Macromolecules, vol. 58, pp. 220-224, 2013.[Abstract]


In this work, the attachment, viability and functionality of rat Blood Outgrowth Endothelial Cells (rBOEC) and genetically modified rBOEC (rBOEC/eNOS-GFP), which over express endothelial nitric oxide synthase (eNOS), were investigated on Poly(lactic acid) (PLA)-chitosan and PLA-chitosan-collagen nanofibrous scaffolds. Both the cell types displayed good attachment, remained viable and functional on both scaffolds. Moreover, incorporation of collagen in the scaffold helped in sustaining the rBOEC for upto one week, although collagen was not found necessary for rBOEC/eNOS-GFP. We conclude that PLA-chitosan based nanofibrous scaffolds can be a potential candidate for BOEC based wound healing applications. © 2013 Elsevier B.V.

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2013

Journal Article

Va Kumar, Bansal, Ga, Patel, Ja, and Mohan, Cab Gopi, “Structure-function prediction of α2A-, α2B-, and α2C-adrenoceptors using homology model assisted antagonist binding study”, Medicinal Chemistry Research, pp. 1-12, 2013.[Abstract]


Abstract: α2A-, α2B-, and α2C-adrenoceptors belong to the rhodopsin-like G-protein coupled receptors family. They are integral membrane proteins typified by a bundle of seven transmembrane helices. 50 % of the currently available drugs in the market target G-protein coupled receptors. Crystal structure of α2A-, α2B-, and α2C-adrenoceptors are not yet solved. We performed homology modeling of the human α2A-, α2B-, and α2C-adrenoceptor subtypes based on the crystal structure of the β2-adrenergic receptor. Molecular docking studies of five different antagonists toward these receptors revealed receptor subtype selectivity, and which in turn potentially guide in the rational design of subtype selective antagonists. Graphical Abstract: [Figure not available: see fulltext.] © 2013 Springer Science+Business Media New York.

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2013

Journal Article

P. T. S. Kumar, Ramya, C., Dr. Jayakumar Rangasamy, Nair, S. K. V., and Lakshmanan, V. - K., “Drug delivery and tissue engineering applications of biocompatible pectin-chitin/nano CaCO3 composite scaffolds”, Colloids and Surfaces B: Biointerfaces, vol. 106, pp. 109-116, 2013.[Abstract]


In this work, we have developed a nanocomposite scaffold using a mixture of pectin, chitin and nano CaCO3 using the technique of lyophilization, with an intended use towards biomedical applications such as tissue engineering and drug delivery. The prepared composite scaffold was characterized using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). In addition, swelling, degradation and biomineralization capability of the composite scaffold was evaluated. The developed composite scaffold showed controlled swelling and degradation in comparison with the control scaffold. Cytocompatibility evaluation of the scaffold was tested on NIH3T3, L929 and human dermal fibroblast (HDF) cells, showed negligible toxicity towards cells. Cell attachment and proliferation studies were also conducted using these cells, which showed that cells attached onto the scaffolds and started to proliferate after 48h of incubation. Further, drug delivery through the scaffold was examined using a bisphosphonate called Fosamax. These results suggest that the developed composite scaffold possess the essential requisites for their application in the fields of tissue engineering and drug delivery. © 2013 Elsevier B.V.

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2013

Journal Article

R. Ranjusha, Prathibha, V., Ramakrishna, S., A. Nair, S., Anjali, P., Subramanian, K. R. V., Sivakumar, N., Kim, T. N., Nair, S. V., and Balakrishnan, A., “Conductive blends of camphoric carbon nanobeads anchored with MnO 2 for high-performance rechargeable electrodes in battery/supercapacitor applications”, Scripta Materialia, vol. 68, pp. 881-884, 2013.[Abstract]


The present study investigates a novel approach by which MnO2 nanoparticle and camphoric carbon nanobead blends are coated on Ti-foils for rechargeable energy storage applications. Depending on the amount of nanocarbon blended onto the MnO2 nanoflake system, these thin film nanocomposite electrodes can exhibit a specific mass capacitance value as high as 1020 F g-1. It has been shown that electrodes based on such a composite system can allow significant room for improvement in the cyclic stability of a rechargeable electrode system.© 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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2013

Journal Article

R. Aparna, Sivakumar, N., Balakrishnan, A., A. Nair, S., Nair, S. V., and Subramanian, K. R. V., “An effective route to produce few-layer graphene using combinatorial ball milling and strong aqueous exfoliants”, Journal of Renewable and Sustainable Energy, vol. 5, 2013.[Abstract]


In this paper, a simple, cost effective, and scalable process for production of few-layer graphene is reported by combining ball milling with exfoliants. The graphene was derived from low-cost graphite, which was subjected to high-energy ball milling in an aqueous medium containing a strong exfoliant (1-pyrenecarboxylic acid) and a common solvent methanol. Such a combinatorial approach has not been used before. At a fixed concentration of 1-pyrenecarboxylic acid, the extent of exfoliation was found to be strongly dependent upon the energy input from the ball milling process (expressed as number of hours of milling) and the solvent used. The graphene produced had the distinctive Raman signature, x-ray diffraction crystallinity, scanning electron microscopic image features, transmission electron microscopic images, and high conductivity values (6.7 × 103 S m-1) in 4-probe electrical measurements all of which compared reasonably with typical values achieved for few-layer graphene. Application of the few-layer graphene was investigated as an electrode for supercapacitors. The graphene-coated electrode showed good specific capacitance and area capacitance (∼176 F g-1 and 1.6 F cm-2), superior to conventionally processed graphene. Also demonstrated is good stability in multiple cyclic voltammetric cycles as also a low fade in capacitance after 100 cycles. Based on the obtained characteristics, which show high degree of fidelity when compared to commercial graphene, the few-layer graphene was considered to be a good cost-effective and scalable alternative for applications in energy and other fields. © 2013 AIP Publishing LLC.

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2013

Journal Article

P. R. Sreerekha, Menon, D., Shantikumar V Nair, and Chennazhi, K. P., “Fabrication of fibrin based electrospun multiscale composite scaffold for tissue engineering applications”, Journal of Biomedical Nanotechnology, vol. 9, pp. 790-800, 2013.[Abstract]


Fabricating scaffolds mimicking the native extracellular matrix (ECM) in both structure and function is a key challenge in the field of tissue engineering. Previously we have demonstrated a novel electrospinnig method for the fabrication of fibrin nanofibers using Poly(vinyl alcohol) (PVA) as an 'electrospinning-driving' polymer. Here we demonstrate the fabrication and characterization of a multiscale fibrin based composite scaffold with polycaprolactone (PCL) by sequential electrospinning of PCL microfibers and fibrin nanofibers. This multiscale scaffold has great potential for tissue engineering applications due to the combined benefits of biological nanofibers such as cell attachment and proliferation and that of microfibers such as open structure, larger pore size and adequate mechanical strength. Physico chemical characterization of the electrospun scaffold was done by Scanning Electron Microscopy (SEM), Contact angle analysis, fibrin specific Phosphotungstic acid haematoxyllin (PTAH) staining and evaluation of mechanical properties. SEM data revealed the formation of bead free nanofibers of fibrin with a fiber diameter ranging from 50-500 nm and microfibers of PCL in the size range of 1 microns to 2.5 microns. These dimensions mimic the hierarchical structure of ECM found in native tissues. Cell attachment and viability studies using human mesenchymal stem cells (hMSC) revealed that the scaffold is non toxic and supports cell attachment, spreading and proliferation. In addition, we examined the inflammatory potential of the scaffold to demonstrate its usefulness in tissue engineering applications. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

J. B. Veluru, Manippady, K. K., Rajendiren, M., K. Mya, M., Rayavarapu, P. R., Nair, S. A., and Seeram, R., “Photocatalytic hydrogen generation by splitting of water from electrospun hybrid nanostructures”, International Journal of Hydrogen Energy, vol. 38, pp. 4324-4333, 2013.[Abstract]


MWCNT-TiO2 hybrid nanostructures are prepared using sol-gel and electrospinning followed by post annealing of as-spun nanofibers at 450°C per 1 h in air. These hybrid nanostructures composed of MWCNTs varied from 0 to 20% (w/w) and are characterized by SEM, TEM, XRD, and FT-IR analysis. MWCNT-TiO2 hybrid structures are utilized in commercially available Methylene blue (MB) dye degradation and found that 2% of MWCNT exhibit superior kinetic constant 6.379 × 10-3 min-1 extracted. In addition, we demonstrate that the doping of MWCTs within TiO2 leads to a significant enhancement of the UV-vis light assisted photocatalytic activity is optimized in comparison with higher (5, 10 and 20%) compositions. UV-vis assisted photocatalytic hydrogen is evolved by photoelectrolytic splitting of water by using MWCNT-TiO2 hybrid nanostructures as electrode. © 2013, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

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2013

Journal Article

S. Maya, Kumar, L. G., Sarmento, B., N. Rejinold, S., Menon, D., Nair, S. V., and Dr. Jayakumar Rangasamy, “Cetuximab Conjugated O-carboxymethyl Chitosan Nanoparticles for Targeting EGFR Overexpressing Cancer Cells”, Carbohydrate Polymers, vol. 93, pp. 661-669, 2013.[Abstract]


Nanoparticle mediated delivery of antineoplastic agents, functionalized with monoclonal antibodies has achieved extraordinary potential in cancer therapy. The objective of this study was to develop a drug delivery system comprising O-carboxymethyl chitosan (O-CMC) nanoparticles, surface-conjugated with Cetuximab (Cet) for targeted delivery of paclitaxel (PTXL) to Epidermal Growth Factor Receptor (EGFR) over-expressing cancer cells. Nanoparticles around 180 ± 35 nm and negatively charged were prepared through simple ionic gelation technique. The alamar blue assay indicated that these targeted nanoparticles displayed a superior anticancer activity compared to non-targeted nanoparticles. The nanoformulation triggered enhanced cell death (confirmed by flow cytometry) due to its higher cellular uptake. The selective uptake of Cet-PTXL-O-CMC nanoparticles by EGFR +VE cancer cells (A549, A431 and SKBR3) compared to EGFR -VE MIAPaCa-2 cells confirms the active targeting and delivery of PTXL via the targeted nanomedicine. Cet-PTXL-O-CMC nanoparticles can be used a promising candidate for the targeted therapy of EGFR over expressing cancers. © 2012 Elsevier Ltd.

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2013

Journal Article

N. Ganesh, Hanna, C., Nair, L. S., and Shantikumar V Nair, “Enzymatically Cross-linked Alginic-hyaluronic Acid Composite Hydrogels as Cell Delivery Vehicles”, International Journal of Biological Macromolecules, vol. 55, pp. 289-294, 2013.[Abstract]


An injectable composite gel was developed from alginic and hyaluronic acid. The enzymatically cross-linked injectable gels were prepared via the oxidative coupling of tyramine modified sodium algiante and sodium hyaluronate in the presence of horse radish peroxidase (HRP) and hydrogen peroxide (H2O2). The composite gels were prepared by mixing equal parts of the two tyraminated polymer solutions in 10U HRP and treating with 1.0% H2O2. The properties of the alginate gels were significantly affected by the addition of hyaluronic acid. The percentage water absorption and storage modulus of the composite gels were found to be lower than the alginate gels. The alginate and composite gels showed lower protein release compared to hyaluronate gels in the absence of hyaluronidase. Even hyaluronate gels showed only approximately 10% protein release after 14 days incubation in phosphate buffer solution. ATDC-5 cells encapsulated in the injectable gels showed high cell viability. The composite gels showed the presence of enlarged spherical cells with significantly higher metabolic activity compared to cells in hyaluronic and alginic acid gels. The results suggest the potential of the composite approach to develop covalently cross-linked hydrogels with tuneable physical, mechanical, and biological properties. © 2013 Elsevier B.V.

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2013

Journal Article

P. R. Sreerekha, Shantikumar V Nair, Chennazhi, K. P., and Menon, D., “Fabrication of Electrospun Poly (lactide-co-glycolide)-fibrin Multiscale Scaffold for Myocardial Regeneration in Vitro”, Tissue Engineering - Part A, vol. 19, pp. 849-859, 2013.[Abstract]


Myocardial tissue engineering is one of the most promising treatment strategies to restore heart function after a massive heart attack. The biomaterials, cells, and scaffold design play important roles in engineering of heart tissue. In this study, we have developed a fibrin-based multiscale electrospun composite scaffold for myocardial regeneration. Fibrin is the natural wound-healing matrix having angiogenic potential and comprehensively used for tissue engineering applications. It provides a natural environment for cell attachment, migration, and proliferation. Morphological, chemical, and mechanical characterization of the scaffolds was done by scanning electron microscopy, fibrin-specific phosphotungstic acid hematoxylin staining, and mechanical testing. The fiber diameters of fibrin nanofibers range from 50 to 300 nm and that of poly (lactide-co-glycolide) microfibers range from 2 to 4 μm, which mimics the structural hierarchy of native myocardial tissue. Our results indicate that this scaffold enhances the differentiation of mesenchymal stem cells into cardiomyocytes. The cardiac phenotype of the cells was confirmed by the presence of cardiac-specific proteins like α-sarcomeric actinin, troponin, tropomyosin, desmin, and atrial natriuretic peptide Estimation of D-Dimer in the culture supernatant for 2 weeks and analysis of scaffold for 3 weeks of in vitro culture of cardiomyocytes indicated the degradation of fibrin and presence of newly synthesized collagen respectively. Our results demonstrate the promising potential of this scaffold for myocardial tissue engineering applications. © Copyright 2013, Mary Ann Liebert, Inc. 2013.

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2013

Journal Article

K. T. Smitha, Anitha, A., Furuike, T., Tamura, H., Nair, S. V., and Dr. Jayakumar Rangasamy, “In Vitro Evaluation of Paclitaxel Loaded Amorphous Chitin Nanoparticles for Colon Cancer Drug Delivery”, Colloids and Surfaces B: Biointerfaces, vol. 104, pp. 245-253, 2013.[Abstract]


Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150 ± 50. nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200 ± 50. nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery. © 2012 Elsevier B.V.

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2013

Journal Article

V. A. Ganesh, Dinachali, S. S., Raut, H. K., Walsh, T. M., Nair, A. S., and Ramakrishna, S., “Electrospun SiO2 nanofibers as a template to fabricate a robust and transparent superamphiphobic coating”, RSC Advances, vol. 3, pp. 3819-3824, 2013.[Abstract]


A one-dimensional morphology of electrospun nanofibers has been used as a template to fabricate a robust and transparent superamphiphobic coating. The template is created by the deposition of a thick layer of SiO2 nanofibers on glass. The developed template (SiO2 nanofibers) is coated with an ultrathin (25 nm) porous silica membrane by the vapor deposition technique. After heat treatment (600 °C), a transparent, superhydrophilic coating consisting of a hybrid silica network (SiO2 nanofibers enclosed by the silica membrane) is obtained. It is observed that during the heat treatment process, the coated silica membrane reinforces the SiO 2 nanofibers and prevents the fibers from disintegrating into nanoparticles, resulting in the formation of a hybrid silica network. The fiber morphology assisted the hybrid silica network to keep its roughness and surface texture. After silanization, the coating exhibited superamphiphobic property with surface contact angles achieved using water and hexadecane are 161° and 146.5°, respectively. This journal is © 2013 The Royal Society of Chemistry.

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2013

Journal Article

Ra Prasanth and Gopinath, Db, “Effect of ZnO nanoparticles on nasopharyngeal cancer cells viability and respiration”, Applied Physics Letters, vol. 102, 2013.[Abstract]


Development of a therapeutic drugs based on nanoparticles requires a better understanding of the mechanism of selective cyto-toxic effects of nanopaticles over cancer cells. Scanning electrochemical microscopy provides opportunity to measure the real time chemical process at cell proximity in the presence of nanoparticle. Herein, the respiration process in nasopharyngeal cancer cells is investigated with the help of scanning electrochemical microscopy. The cell viability has been tested with MTT assay. The results show that ZnO nanoparticles have time and dose dependent effect in nasopharyngeal cancer cells and the cell respiration rate decreases with time. © 2013 American Institute of Physics.

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2013

Journal Article

V. A. Ganesh, Dinachali, S. S., Nair, A. S., and Ramakrishna, S., “Robust superamphiphobic film from electrospun TiO2 nanostructures”, ACS Applied Materials and Interfaces, vol. 5, pp. 1527-1532, 2013.[Abstract]


Rice-shaped TiO2 nanostructures are fabricated by electrospinning for creating a robust superamphiphobic coating on glass substrates. The as-fabricated TiO2 nanostructures (sintered at 500 C) are superhydrophilic in nature which upon silanization turn into superamphiphobic surface with surface contact angle (SCA) values achieved using water (surface tension, γ = 72.1 mN/m) and hexadecane (surface tension, γ = 27.5 mN/m) being 166 and 138.5, respectively. The contact angle hysteresis for the droplet of water and hexadecane are measured to be 2 and 12, respectively. Thus, we have successfully fabricated superior self-cleaning coatings that possess exceptional superamphiphobic property by employing a simple, cost-effective, and scalable technique called electrospinning. Furthermore, the coating showed good mechanical and thermal stability with strong adherence to glass surface, thus revealing the potential for real applications. © 2013 American Chemical Society.

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2013

Journal Article

A. Paravannoor, Ranjusha, R., Sivakumar, N., Asha, A. M., Kim, T. N., Shantikumar V Nair, Vani, R., Kalluri, S., Balakrishnan, A., and Subramanian, K. R. V., “Chemical and Structural Stability of Porous Thin Film NiO Nanowire Based Electrodes for Supercapacitors”, Chemical Engineering Journal, vol. 220, pp. 360-366, 2013.[Abstract]


Nanowires of NiO were successfully synthesized using a simple hydrothermal route. The nanowires were characterized for phase composition and morphology by X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques, respectively. XRD analysis showed that the powders produced were of high purity cubic NiO phase. Selected area electron diffraction (SAED) analysis during TEM showed the growth direction of NiO nanowires in (100), while exhibiting an average diameter of ∼ 65nm. BET analysis showed these nanowires exhibiting a surface area of 153.2m2/g. These nanowires were electrophoretically deposited on titanium foils as thin layer (∼5μm thickness) and were studied for their capacitive behavior as electrodes for supercapacitor applications. Image analysis and atomic force microscopy (AFM) studies revealed the thin film coating to be highly porous (&gt;50%). Cyclic voltammetry (CV) studies on these electrodes exhibited a specific mass capacitance of 750F/g with 12% capacitance fade at the end of 1000 cycles. The present study elucidates how NiO surface morphology and OH- adsorption/desorption behaviors underlying these electrodes impact the chemical and structural stability performance. © 2013 Elsevier B.V.

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2013

Journal Article

S. Sasidharan, Jayasree, A., Fazal, S., Koyakutty, M., Shantikumar V. Nair, and Menon, D., “Ambient temperature synthesis of citrate stabilized and biofunctionalized, fluorescent calcium fluoride nanocrystals for targeted labeling of cancer cells”, Biomaterials Science, vol. 1, pp. 294-305, 2013.[Abstract]


Targeted biological contrast agents are emerging as promising candidates in the field of cancer theragnostics. Herein, we report an ambient temperature synthesis of a nanosized, antibody functionalized lanthanide doped CaF 2 biolabel and demonstrate in vitro its potential for cancer cell targeting efficacy and specificity. Monodispersed citrate stabilized lanthanide (Eu3+) doped CaF2 nanoparticles with size ∼25 nm, exhibiting strong fluorescent emission at 612 nm, were prepared using an aqueous wet chemical route at room temperature. Biofunctionalization of the fluorescent nanoparticles using an anti-EGFR antibody through EDC-NHS coupling chemistry enabled targeting of EGFR over-expressing cells. The nanobioconjugates showed preferential binding to EGFR+ve oral epithelial carcinoma cells (KB) and human epidermoid carcinoma cells (A431) with no accumulation onto EGFR -ve non-cancerous NIH 3T3 cells. The fluorescence was maintained after the bioconjugation as well as after attachment to the cancer cells, demonstrating their potential as targeted biolabels. Cytotoxicity evaluation with several cancerous (A431, KB) and non-cancerous (NIH 3T3, L929) cell lines revealed no toxicity at concentrations up to 1 mM. Thus, the fluorescence characteristics and biocompatibility, coupled with the molecular receptor targeting capability, suggest the potential use of CaF2 in the field of bioimaging. © 2013 The Royal Society of Chemistry.

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2013

Journal Article

K. T. Shalumon, Sowmya, S., Sathish, D., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Effect of incorporation of nanoscale bioactive glass and hydroxyapatite in PCL/chitosan nanofibers for bone and periodontal tissue engineering”, Journal of Biomedical Nanotechnology, vol. 9, pp. 430-440, 2013.[Abstract]


A biomimetic scaffold which can very closely mimic the extracellular matrix of the bone was fabricated by incorporating nano-bioceramic particles such as nano bioglass (nBG) and nano hydroxyapatite (nHAp) within electrospun nanofibrous scaffold. A comparative study between nHAp incorporated poly(caprolactone) (PCL)-chitosan (CS) and nBG incorporated PCL-CS nanofibrous scaffolds was carried out and their feasibility in tissue engineering was investigated. All the samples were optimized to obtain fibers of similar diameter from 100-200 nm for the ease of comparison between the samples. Protein adsorption studies showed that PCL-CS incorporated with 3 wt% nHAp and 3 wt% nBG adsorbed more proteins on their surface than other samples. Cell attachment and proliferation studies using human periodontal ligament fibroblast cells (hPLFs) and osteoblast like cells (MG-63 cell lines) showed that nBG incorporated samples are slightly superior to nHAp incorporated counterparts. Cell viability test using alamar blue assay and live/dead staining confirms that the scaffolds are cytocompatible. ALP activity confirmed the osteoblastic behavior of hPDLFs. Also the presence of nHAp and nBG enhanced the ALP activity of hPDLF on the PCH3 and PCB3 scaffolds. These studies indicate that nBG incorporated electrospun scaffolds are comparatively better candidates for orthopedic and periodontal tissue engineering applications. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

A. Anitha, Uthaman, S., Shantikumar V. Nair, Dr. Jayakumar Rangasamy, and Lakshmanan, V. - K., “Enhanced delivery system of flutamide loaded chitosan-dextran sulphate nanoparticles for prostate cancer”, Journal of Biomedical Nanotechnology, vol. 9, pp. 335-347, 2013.[Abstract]


In the current work, a sustained drug delivery system of flutamide (FLT) was developed using chitosan (CS) and dextran sulphate (DS) nanoparticles and were characterized using different techniques. The prepared nanoparticles showed a size of 80-120 nm with an entrapment efficiency of 55±6.95%. In addition, blood compatibility, in vitro cytotoxicity, drug release and cellular uptake studies were also carried out. The drug release studies showed a sustained and pH dependent release pattern as a result, after 120 h about 66% drug release occurred at pH 7.4 and 78% release occurred in acidic pH. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) experiments proved the preferential toxicity of drug loaded nanoparticles towards prostate cancer cells (PC3) unlike in normal cells, mouse fibroblast cells (L929). The cell death mechanism of drug loaded nanoparticles for a concentration of 50 and 75 nM showed 28±2 and 35.2±4% apoptosis in samples treated with the PC3 cells after 24 h. Fluorescent microscopic imaging and flow cytometry confirmed the preferential uptake of the nanoparticles (NPs) in the prostate cancer cells (PC3) unlike in normal (L929) cells. Hence the developed FLT loaded CS-DS NPs could be used as a promising system for controlled delivery in prostate cancer. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

Aa Licciulli, Chiechi, Aa, Fersini, Ma, Sanosh, K. Pa, and Balakrishnan, Ab, “Influence of zirconia interfacial coating on alumina fiber-reinforced alumina matrix composites”, International Journal of Applied Ceramic Technology, vol. 10, pp. 251-256, 2013.[Abstract]


The present study demonstrates an approach for fabricating fiber-reinforced ceramic matrix composites (CMCs) involving the coating of 2-dimensional woven alumina fibers with zirconia layer by sol gel, followed by impregnation of these coated fibers with alumina matrix and pressureless sintering. To emphasize the benefits of the zirconia coating on these CMCs, a reference sample without interfacial coating layer was prepared. The zirconia-coated CMCs showed superior flexural strength and thermal shock resistance compared with their uncoated counterparts. Foreign object damage tests carried out on the ZrO2 coated CMCs at high impact speed showed localized damage without any shattering. © 2012 The American Ceramic Society.

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2013

Journal Article

S. Sivasundar, Oommen, A. T., Prakash, O., Baskaran, S., Dr. Raja Biswas, Nair, S., Dr. Gopi Mohan C., and Biswas, L., “Molecular defect of 'Prothrombin Amrita': Substitution of arginine by glutamine (Arg553 to Gln) near the Na+ binding loop of prothrombin”, Blood Cells, Molecules, and Diseases, vol. 50, pp. 182-183, 2013.[Abstract]


Prothrombin, the precursor to thrombin, is a serine protease that plays a key role in hemostasis and thrombosis. Several studies have reported mutations resulting from the deletion, substitution, or insertion of a single nucleotide in the prothrombin gene that lead to hypoprothrombinemia, dysprothrombinemia, or thrombosis [1]. One of the most common genetic variations predisposing to deep venous thrombosis is a polymorphism in the factor V gene (Arg506Gln) resulting in the factor V Leiden mutation. Transition of guanine to adenine at nucleotide position 20210 in the 3′ untranslated region of the prothrombin gene is the second most common genetic risk factor for venous thrombosis, which we diagnose in approximately 50 patients annually in Amrita hospital. Several other mutations in the prothrombin gene that are associated with the thrombosis have been reported. The eponym of some of the prothrombin point mutations identified globally are — Padua (Arg271 to His), Corpus Christi (Arg382 to Cys), Obhiro (Arg271 to Cys), Barcelona (Arg273 to Cys), San Antonio (Arg320 to His), Himi (Met337 to Thr and Arg388 to His), Denver (Arg457 to Gln), Dhahran (Arg271 to His), Clamart (Arg320 to Ile), Segovia (Gly319 to Arg), Vellore 1 (Ala362 to Thr), Perijaá (Gly548 to Ala), Himi (Arg388 to His and Met337 to Thr), Habana, Poissy, Houston, Salakta, Thrombin Greenvillae (Arg517 to Gln), etc.

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2013

Journal Article

B. S. Anisha, Sankar, D., Mohandas, A., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Chitosan-hyaluronan/nano chondroitin sulfate ternary composite sponges for medical use”, Carbohydrate Polymers, vol. 92, pp. 1470-1476, 2013.[Abstract]


In this work chitosan-hyaluronan composite sponge incorporated with chondroitin sulfate nanoparticle (nCS) was developed. The fabrication of hydrogel was based on simple ionic cross-linking using EDC, followed by lyophilization to obtain the composite sponge. nCS suspension was characterized using DLS and SEM and showed a size range of 100-150 nm. The composite sponges were characterized using SEM, FT-IR and TG-DTA. Porosity, swelling, biodegradation, blood clotting and platelet activation of the prepared sponges were also evaluated. Nanocomposites showed a porosity of 67% and showed enhanced swelling and blood clotting ability. Cytocompatibility and cell adhesion studies of the sponges were done using human dermal fibroblast (HDF) cells and the nanocomposite sponges showed more than 90% viability. Nanocomposite sponges also showed enhanced proliferation of HDF cells within two days of study. These results indicated that this nanocomposite sponges would be a potential candidate for wound dressing. © 2012 Elsevier Ltd.

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2013

Journal Article

Nab Sivakumar, “Influence of structural ordering on electrical conductivity of nanostructured manganese zinc ferrite”, Materials Chemistry and Physics, vol. 138, pp. 102-107, 2013.[Abstract]


In the present study, nanostructured manganese zinc ferrite of 11 nm grain size was synthesized by co-precipitation technique and subsequently suitably heat treated to obtain higher grain sizes. The plot of temperature dependence of dc conductivity shows the semiconducting nature of samples. The observed changes in the electrical conductivity have been attributed with the influence of structural ordering upon annealing. The observed decrease in conductivity when the grain size is increased from 11 to 69 nm upon annealing is clearly due to the structural ordering which is evident from FESEM. © 2012 Elsevier B.V. All rights reserved.

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2013

Journal Article

M. Annapoorna, Kumar, P. T. Sudheesh, Lakshman, L. R., Lakshmanan, V. - K., Nair, S. V., and Dr. Jayakumar Rangasamy, “Biochemical properties of Hemigraphis alternata incorporated chitosan hydrogel scaffold”, Carbohydrate Polymers, vol. 92, pp. 1561-1565, 2013.[Abstract]


In this work, Hemigraphis alternata extract incorporated chitosan scaffold was synthesized and characterized for wound healing. The antibacterial activity of Hemigraphis incorporated chitosan scaffold (HIC) against Escherichia coli and Staphylococcus aureus was evaluated which showed a reduction in total colony forming units by 45-folds toward E. coli and 25-fold against S. aureus respectively. Cell viability studies using Human Dermal Fibroblast cells (HDF) showed 90% viability even at 48 h when compared to the chitosan control. The herbal scaffold made from chitosan was highly haemostatic and antibacterial. The obtained results were in support that the herbal scaffold can be effectively applied for infectious wounds. © 2012 Elsevier Ltd.

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2013

Journal Article

P. T. Sudheesh Kumar, Lakshmanan, V. - K., Raj, M., Dr. Raja Biswas, Hiroshi, T., Nair, S. V., and Dr. Jayakumar Rangasamy, “Evaluation of Wound Healing Potential of β-chitin Hydrogel/nano zinc Oxide Composite Bandage”, Pharmaceutical Research, vol. 30, pp. 523-537, 2013.[Abstract]


Purpose: β-chitin hydrogel/nZnO composite bandage was fabricated and evaluated in detail as an alternative to existing bandages. Methods: β-chitin hydrogel was synthesized by dissolving β-chitin powder in Methanol/CaCl2 solvent, followed by the addition of distilled water. ZnO nanoparticles were added to the β-chitin hydrogel and stirred for homogenized distribution. The resultant slurry was frozen at 0 C for 12 h. The frozen samples were lyophilized for 24 h to obtain porous composite bandages. Results: The bandages showed controlled swelling and degradation. The composite bandages showed blood clotting ability as well as platelet activation, which was higher when compared to the control. The antibacterial activity of the bandages were proven against Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli). Cytocompatibility of the composite bandages were assessed using human dermal fibroblast cells (HDF) and these cells on the composite bandages were viable similar to the Kaltostat control bandages and bare β-chitin hydrogel based bandages. The viability was reduced to 50-60% in bandages with higher concentration of zinc oxide nanoparticles (nZnO) and showed 80-90% viability with lower concentration of nZnO. In vivo evaluation in Sprague Dawley rats (S.D. rats) showed faster healing and higher collagen deposition ability of composite bandages when compared to the control. Conclusions: The prepared bandages can be used on various types of infected wounds with large volume of exudates. © 2012 Springer Science+Business Media New York.

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2013

Journal Article

P. T. S. Kumar, Raj, N. M., Praveen, G., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “In vitro and in vivo evaluation of microporous chitosan hydrogel/nanofibrin composite bandage for skin tissue regeneration”, Tissue Engineering - Part A, vol. 19, pp. 380-392, 2013.[Abstract]


In this work, we have developed chitosan hydrogel/nanofibrin composite bandages (CFBs) and characterized using Fourier transform-infrared spectroscopy and scanning electron microscopy. The homogeneous distribution of nanofibrin in the prepared chitosan hydrogel matrix was confirmed by phosphotungstic acid-hematoxylin staining. The mechanical strength, swelling, biodegradation, porosity, whole-blood clotting, and platelet activation studies were carried out. In addition, the cell viability, cell attachment, and infiltration of the prepared CFBs were evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblast (HDF) cells. It was found that the CFBs were microporous, flexible, biodegradable, and showed enhanced blood clotting and platelet activity compared to the one without nanofibrin. The prepared CFBs were capable of absorbing fluid and this was confirmed when immersed in phosphate buffered saline. Cell viability studies on HUVECs and HDF cells proved the nontoxic nature of the CFBs. Cell attachment and infiltration studies showed that the cells were found attached and proliferated on the CFBs. In vivo experiments were carried out in Sprague-Dawley rats and found that the wound healing occurred within 2 weeks when treated with CFBs than compared to the bare wound and wound treated with Kaltostat. The deposition of collagen was found to be more on CFB-treated wounds compared to the control. The above results proved the use of these CFBs as an ideal candidate for skin tissue regeneration and wound healing. © Copyright 2013, Mary Ann Liebert, Inc.

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2013

Journal Article

E. Ja Levorson, Sreerekha, PbRaman, Chennazhi, K. Pb, Kasper, F. Ka, Nair, S. Vb, and Mikos, A. Gac, “Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration”, Biomedical Materials (Bristol), vol. 8, 2013.[Abstract]


Recently, scaffolds for tissue regeneration purposes have been observed to utilize nanoscale features in an effort to reap the cellular benefits of scaffold features resembling extracellular matrix (ECM) components. However, one complication surrounding electrospun nanofibers is limited cellular infiltration. One method to ameliorate this negative effect is by incorporating nanofibers into microfibrous scaffolds. This study shows that it is feasible to fabricate electrospun scaffolds containing two differently scaled fibers interspersed evenly throughout the entire construct as well as scaffolds containing fibers composed of two discrete materials, specifically fibrin and poly(ε-caprolactone). In order to accomplish this, multiscale fibrous scaffolds of different compositions were generated using a dual extrusion electrospinning setup with a rotating mandrel. These scaffolds were then characterized for fiber diameter, porosity and pore size and seeded with human mesenchymal stem cells to assess the influence of scaffold architecture and composition on cellular responses as determined by cellularity, histology and glycosaminoglycan (GAG) content. Analysis revealed that nanofibers within a microfiber mesh function to maintain scaffold cellularity under serum-free conditions as well as aid the deposition of GAGs. This supports the hypothesis that scaffolds with constituents more closely resembling native ECM components may be beneficial for cartilage regeneration. © 2013 IOP Publishing Ltd.

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2013

Journal Article

H. K. Raut, Nair, A. S., Dinachali, S. S., Ganesh, V. A., Walsh, T. M., and Ramakrishna, S., “Porous SiO2 anti-reflective coatings on large-area substrates by electrospinning and their application to solar modules”, Solar Energy Materials and Solar Cells, vol. 111, pp. 9-15, 2013.[Abstract]


Fabrication of large-area anti-reflective coatings (ARCs) on glass substrates by using a cost-efficient and simple approach, especially for applications in photovoltaics, remains a challenge. This study proposes electrospinning as a technique to fabricate porous SiO2 ARCs on large-area glass substrates (20×20 cm2). The existing electrospinning setup is modified to enable large-area glass coatings and electrospinning process parameters are optimized to achieve sub-wavelength ARCs. The post-sintered SiO2 ARC is thoroughly characterized for the film morphology and optical properties. The transmittance for one-side and both-sides coated glass is found to be 94.3% and 96% respectively. The anti-reflective glass is incorporated in solar modules to determine the increase in short circuit current. The increase in short-circuit current is found to be 3%. Electrospinning as a fabrication technique has potential in offering a cost effective solution for synthesizing ARCs on large-area substrates for photovoltaic applications. © 2012 Elsevier B.V.

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2013

Journal Article

Dr. Sabitha M., N. Rejinold, S., Nair, A., Lakshmanan, V. - K., Nair, S. V., and Dr. Jayakumar Rangasamy, “Development and Evaluation of 5-fluorouracil Loaded Chitin Nanogels for Treatment of Skin Cancer”, Carbohydrate Polymers, vol. 91, pp. 48-51, 2013.[Abstract]


This study focuses on development and evaluation of 5-fluorouracil (5-FU) loaded chitin nanogels (FCNGs). It formed good, stable aqueous dispersion with spherical particles in 120-140 nm size range and showed pH responsive swelling and drug release. The FCNGs showed toxicity on melanoma (A375) in a concentration range of 0.4-2.0 mg/mL, but less toxicity toward human dermal fibroblast (HDF) cells by MTT assay. Confocal analysis revealed uptake of FCNGs by both cells. From skin permeation experiments, FCNGs showed almost same steady state flux as that of control 5-FU but the retention in the deeper layers of skin was found to be 4-5 times more from FCNGs. Histopathological evaluation revealed loosening of the horny layer of epidermis by interaction of cationically charged chitin, with no observed signs of inflammation and so FCNGs can be a good option for treatment of skin cancers. © 2012 Elsevier Ltd.

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2013

Journal Article

N. Mohammed, N. Rejinold, S., Mangalathillam, S., Dr. Raja Biswas, Nair, S. V., Dr. Jayakumar Rangasamy, and Dr. Sabitha M., “Fluconazole Loaded Chitin Nanogels as a Topical Ocular Drug Delivery Agent for Corneal Fungal Infections”, Journal of Biomedical Nanotechnology, vol. 9, pp. 1521-1531, 2013.[Abstract]


Poor bioavailability of antifungal drugs due to the various protective mechanisms of the eye is a serious concern for the treatment of corneal fungal infections in today's world. The use of nanosystems that can improve the bioavailability of these antifungal drugs is relatively a new idea being conceived and here we have synthesized fluconazole loaded chitin nanogels (Flu-CNGs) which can be used for the treatment of corneal fungal infections. These nanogels were characterized using DLS, Zeta potential, SEM, FTIR and TG/DTA. The prepared Flu-CNGs have controlled release pattern which is ideal for the continuous availability of fluconazole over a longer period of time for an effective fungal treatment. Flu- CNGs are haemocompatible, cytocompatible and also showed very good cell uptake in human dermal fibroblast cells and penetration to the deeper sections of the porcine cornea with no signs of destruction or inflammation to corneal cells as shown in ex vivo permeation studies. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

V. Aa Kumar, Steffy, Ka, Chatterjee, Mb, Sugumar, Mc, Dinesh, K. Ra, Manoharan, Ac, Karim, Sa, and Dr. Raja Biswas, “Detection of oxacillin-susceptible mecA-positive Staphylococcus aureus isolates by use of chromogenic medium MRSA ID”, Journal of Clinical Microbiology, vol. 51, pp. 318-319, 2013.[Abstract]


Reports of oxacillin-susceptible mecA-positive Staphylococcus aureus strains are on the rise. Because of their susceptibility to oxacillin and cefoxitin, it is very difficult to detect them by using routine phenotypic methods. We describe two such isolates that were detected by chromogenic medium and confirmed by characterization of the mecA gene element. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

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2013

Journal Article

P. La Benitez, Sweet, J. Ab, Fink, Hc, Chennazhi, K. Pd, Nair, S. Vd, Enejder, Ac, and Heilshorn, S. Ce, “Sequence-Specific Crosslinking of Electrospun, Elastin-Like Protein Preserves Bioactivity and Native-Like Mechanics”, Advanced Healthcare Materials, vol. 2, pp. 114-118, 2013.[Abstract]


A nanoscale mimic of the extracellular matrix is electrospun from a highly tunable family of elastin-like proteins. A sequence-specific, two-step crosslinking procedure is developed to preserve the nanofiber morphology, elastin-like mechanics, and specific bioactivity. Rodent marrow stromal cells show sequence-specific adhesion on the matrices, which are imaged using label-free coherent anti-Stokes Raman scattering (CARS) microscopy. © 2013 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.

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2013

Journal Article

T. R. Anuraj, N Rejinold, S., Biswas, R., Saroj, S., Shantikumar V Nair, Dr. Jayakumar Rangasamy, and Dr. Sabitha M., “Curcumin Nanospheres by Surfactant Free Wet Milling Method (In Press)”, Journal of Biomedical Nanotechnology, 2013.

2013

Journal Article

S. Chandran, Praveen, G., Snima, K. S., Pavithran, K., Chennazhi, K., Lakshmanan, V. K., and Shantikumar V Nair, “Potential use of drug loaded nano composite pectin scaffolds for the treatment of ovarian cancer.”, Current drug delivery, vol. 10, pp. 326-335, 2013.[Abstract]


Ovarian cancer is the ninth most common cancer amongst women and ranked as fifth in terms of the cause of cancer related mortality accounting for more deaths than any other cancer of the female reproductive system. Gemcitabine is the most common chemotherapeutic agent used in the treatment of ovarian cancer despite of its disadvantage of having a very lesser half life. In this study, we have envisaged the use of a highly porous, biomimetic and implantable pectin scaffold embedded with gemcitabine loaded fibrin nanoconstructs to improve the half life of the drug, thereby providing localized therapy for ovarian cancer. The controlled and sustained release of the chemokine from the scaffold system was extensively analyzed in vitro different pH environments. The composite scaffolds were found to be highly biocompatible when tested with mammalian cell lines. The excellent cytotoxicity and apoptosis responses induced in ovarian cancer, PA- 1 cell lines proved that the nanocomposite Pectin scaffolds loaded with specific chemokine can be used as implantable "therapeutic wafers" for distracting metastatic cancer cells and thus improve the survival rate of ovarian cancer afflicted individuals.

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2013

Journal Article

N. S. Rejinold, Baby, T., Nair, S. V., and Dr. Jayakumar Rangasamy, “Paclitaxel loaded fibrinogen coated CDTE/ZNTE core shell nanoparticles for targeted imaging and drug delivery to breast cancer cells”, Journal of Biomedical Nanotechnology, vol. 9, pp. 1657-1671, 2013.[Abstract]


The study aims at the targeted imaging using CdTe/ZnTe core shell QDs and delivery of paclitaxel (PTX) loaded fibrinogen coated yellow-QDs (PTX-fib-yellow-QDs) towards breast cancer cells via the α5 β1 -integrins. We developed fibrinogen coated different sized CdTe/ZnTe core shell quantum dots of 2-10 nm size, which have been prepared by one-pot aqueous-phase approach. The fib-coated-QDs (fib-coated-QDs) and PTX-fib-yellow-QDs were prepared by twostep coacervation technique using CaCl2 as cross-linker. Particle size of fib-coated-QDs was in between 60-220 nm while PTX-fib-yellow-QDs showed 180 ± 40 nm. The MTT assay confirmed cytocompatibility of fib-coated-QDs on L929 and MCF-7 than bare QDs, whereas significant toxicity toward MCF-7 by PTX-fib-yellow-QDs was observed. The hemocompatible fib-coated-QDs showed enhanced localization and retention toward α5 β1 -integrins +ve MCF-7 compared to α5 β1 -integrins -ve L929 cells. The specific binding of fib-coated-yellow-QDs was further confirmed with α5 β1 -integrins +ve HeLa and α5 β1 -integrins -ve HT29 cells. Cellular uptake studies revealed localization of PTX-fib-coated-yellow-QDs inside MCF-7 cells compared to the normal L929 cells. These results indicated that fib-coated-QDs could be used for targeted imaging and as a suitable "nanocarrier" aiming breast cancer cells. Copyright © 2013 American Scientific Publishers All rights reserved.

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2013

Journal Article

R. Murugan, Babu, V. J., Khin, M. M., Nair, A. S., and Ramakrishna, S., “Synthesis and photocatalytic applications of flower shaped electrospun ZnO-TiO2 mesostructures”, Materials Letters, vol. 97, pp. 47-51, 2013.[Abstract]


We report the synthesis, characterization and photocatalytic application of ZnO-TiO2 electrospun materials. Flower shaped ZnO-TiO2 mesostructures were synthesized using an electrospinning technique, which is a well established and cost effective method for large scale production of 1-D nanomaterials. Calcination of the obtained electrospun ZnO-TiO2 nanofiber membrane was done in a furnace at 500 °C. Photodegradation of alizarin red S (ARS) was examined individually using ZnO (NPs), TiO2 (P25) and ZnO-TiO2 flowers. A comparison of the photocatalytic performance of the material with TiO2 (P25) and ZnO (NPs) showed that the nanoflower shaped structures were superior to commercially available P25 and ZnO (NPs). We expected that the material would have wide range of potential applications such as chemosensors, photonic crystals, UV-vis blockers, self-cleaning and organic synthesis. © 2013 Elsevier B.V.

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2013

Journal Article

L. Singh, Rai, U. S., Rai, A. Kumar, and Mandal, K. D., “Sintering effects on dielectric properties of Zn-doped CaCu3Ti4O12 ceramic synthesized by modified sol-gel route”, Electronic Materials Letters, vol. 9, pp. 107–113, 2013.[Abstract]


CaCu2.90Zn0.10Ti4O12 ceramic was synthesized by a novel semi-wet route and calcined at 800°C in air for 8 h. The obtained powder was divided into three parts and sintered in air at 950°C for 6 h, 8 h, and 12 h, separately. XRD results confirmed the single phase formation of all the sintered samples with similar cubic structure of CaCu3Ti4O12 (CCTO). Scanning electron micrographs of the CaCu2.9Zn0.1Ti4O12 ceramic sintered for 6 h shows bimodal grain size distribution. Increasing the sintering time significantly promotes the grain growth and microstructural densification. The sintering duration was found to have tremendous influence on microstructure and dielectric properties of CaCu2.90Zn0.10Ti4O12 ceramic. The CaCu2.9Zn0.1Ti4O12 ceramic sintered for 12 h exhibited high dielectric constant $ε$ r ∼ 5971 at 1 kHz and room temperature. It is found that $ε$ r is independent at high frequency and weakly dependent on temperature.

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2013

Journal Article

L. Singh, Rai, U. S., Rai, A. Kumar, and Mandal, K. D., “Dielectric behavior of CaCu3Ti4O12 electro-ceramic doped with La, Mn and Ni synthesized by modified citrate-gel route”, Journal of Advanced Ceramics, vol. 2, pp. 119–127, 2013.[Abstract]


The effect of La3+, Mn2+ and Ni2+ doped calcium copper titanate, CaCu3Ti4O12 (CCTO), at higher concentrations (CR1 and CR2 with 5 mol% and 10 mol%, respectively), has been examined by semi-wet route at relatively lower temperature. This semi-wet route employs citrate-nitrate gel chemical method using TiO2 solid powders. X-ray diffraction (XRD) analysis confirms the formation of single phase in the doped samples sintered at 900 °C for 8 h. Scanning electron micrographs (SEM) show that the average grain size for CR2 is larger than that of CR1 composition. The energy dispersive X-ray spectroscopy (EDX) is used to study the percentage compositions of different ions present in both ceramics. Dielectric constant (ɛ r) and dielectric loss (tan$δ$) values of CR1 are comparatively higher than those of CR2 ceramic at all measured frequencies and temperatures. The nature of temperature-dependent relaxation behavior of the ceramics is also studied by impedance, modulus spectroscopic analysis and confirms Maxwell-Wagner relaxation.

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2013

Journal Article

L. R. Lakshman, Kumar, P. T., Nair, S. V., Nair, S. V., and Jayakumar, R., “Chitosan sponge containing the herb coleus plectranthus as a wound dressing”, Journal of Chitin and Chitosan Science, vol. 1, pp. 13–20, 2013.[Abstract]


Coleus plectranthus, an herbal extract is an excellent wound healing agent for both acute and chronic wounds. Its anti-inflammatory property would be helpful to prevent scar formation. In this work, we developed coleus plectranthus herb extract incorporated chitosan sponge for wound healing applications. The morphology analysis of the prepared sponges was done by SEM analysis. The herb incorporated chitosan sponge showed high swelling ability in comparison to the conventional sponge. The protein adsorption ability of the prepared sponge was evaluated and the data proved the enhanced protein adsorption capability of the sponges. The sponges showed excellent antibacterial activity against Staphylococcus aureus, Klebsiella sp. and Acinetobacter sp. The cytocompatibility of the herb incorporated sponge was studied by cell cycle analysis and cell viability assay. These results showed that the sponges were cytocompatible and promote cellular growth.

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2013

Journal Article

Dr. Bindhu Paul, Bhandari, R. K., Kobayashi, T., Horiguchi, R., Kobayashi, Y., Nakamoto, M., Shibata, Y., Sakai, F., Nakamura, M., and Nagahama, Y., “Estrogen oversees the maintenance of the female genetic program in terminally differentiated gonochorists”, Scientific reports, vol. 3, p. 2862, 2013.[Abstract]


The sexual plasticity of the gonads is not retained after the completion of sex differentiation in vertebrates, except in some hermaphroditic species. Here, we report that the depletion of estradiol-17β (E2) by aromatase inhibitors (AI) for up to six months resulted in a functional female-to-male sex reversal in sexually-mature adults of two gonochoristic fish species, Nile tilapia and medaka. The sex-reversed fish showed a typical male pattern of E2 and androgen levels, secondary sexual characteristics, and male-like sex behavior, producing fertile sperm. Conversely, co-treatment of E2 inhibited AI-induced sex reversal. In situ hybridization of medaka gonads during AI-induced sex reversal indicated that cysts on the dorsal side of the adult ovaries are the origin of germ cells and Sertoli cells in the newly formed testicular tissue. Gonochoristic fish maintain their sexual plasticity until adulthood and E2 plays a critical role in maintaining the female phenotype. More »»

2013

Journal Article

B. Swarnalatha, Nair, S. L., Shalumon, K. T., Milbauer, L. C., Dr. Jayakumar Rangasamy, Dr. Bindhu Paul, Menon, K. K., Hebbel, R. P., Somani, A., and Shantikumar V. Nair, “Poly (lactic acid)–chitosan–collagen composite nanofibers as substrates for blood outgrowth endothelial cells”, International Journal of Biological Macromolecules, vol. 58, pp. 220 - 224, 2013.[Abstract]


Abstract In this work, the attachment, viability and functionality of rat Blood Outgrowth Endothelial Cells (rBOEC) and genetically modified rBOEC (rBOEC/eNOS-GFP), which over express endothelial nitric oxide synthase (eNOS), were investigated on Poly(lactic acid) (PLA)–chitosan and PLA–chitosan–collagen nanofibrous scaffolds. Both the cell types displayed good attachment, remained viable and functional on both scaffolds. Moreover, incorporation of collagen in the scaffold helped in sustaining the rBOEC for upto one week, although collagen was not found necessary for rBOEC/eNOS-GFP. We conclude that PLA–chitosan based nanofibrous scaffolds can be a potential candidate for \{BOEC\} based wound healing applications. More »»

2013

Journal Article

H. Zhao, Guan, G., Duan, J., Cheng, N., Wang, J., Matsuda, M., Dr. Bindhu Paul, and Nagahama, Y., “Ol4E-T, a Eukaryotic Translation Initiation Factor 4E-Binding Protein of Medaka Fish (Oryzias latipes), Can Interact With Nanos3 and Vasa In Vitro”, Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, vol. 320, pp. 10–21, 2013.[Abstract]


Maternal factors have essential roles in the specification and development of germ cells in metazoans. In Drosophila, a number of genes such as oskar, vasa, nanos, and tudor are required for specific steps in pole cell formation and further germline development. Drosophila cup, another maternal factor, is confirmed as a main factor in normal oogenesis, maintenance, and survival of female germ-line stem cells by interaction with Nanos. Through searching for the homolog of Drosophila cup in the medaka, the homolog of eukaryotic translation initiation factor 4E (eIF4E)-transporter, named Ol4E-T, was identified. Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization revealed that Ol4E-T is maternally deposited in the embryo and Ol4E-T expression is maintained throughout embryogenesis. Ol4E-T is predominantly expressed in the adult gonads. In the testes, Ol4E-T is expressed in the same regions where medaka vasa, named olvas is expressed. In the ovary, expression of Ol4E-T conforms to that of nanos3 and olvas. Ol4E-T harbors a well-conserved eIF4E-binding motif, YTKEELL, by which Ol4E-T interacts with eIF4E in medaka. Additionally, Ol4E-T can interact with medaka Nanos3 and Olvas, as shown by yeast two hybridization. The spatial expression and interactions between Ol4E-T with germ cell markers Olvas and Nanos3 suggest a role for Ol4E-T in germ-line development in medaka. J. Exp. Zool. (Mol. Dev. Evol.) 320B:10–21, 2013. © 2012 Wiley Periodicals, Inc. More »»

2013

Journal Article

V. Anil Kumar, Nair, N., Thachathodiyl, R., Nandakumar, A., Dinesh, K. R., Thatcher, E., Karim, S., and Dr. Raja Biswas, “Molecular characterization of methicillin-resistant staphylococcus aureus causing fatal purulent pericarditis”, Journal of laboratory physicians, vol. 5, p. 136, 2013.[Abstract]


Though pericardial disease is common in patients with renal disease, purulent pericarditis is very rare. We report a fatal case of purulent pericarditis and sepsis due to methicillin-resistant Staphylococcus aureus in a 78-year-old male with systemic hypertension and renal disease along with the molecular characterization of its resistant mechanism. More »»

2013

Journal Article

A. A1, V, J., P, S., and Dr. Gopi Mohan C., “Uridine monophosphate kinase as potential target for tuberculosis: from target to lead identification”, Interdisciplinary Sciences: Computational Life Sciences (Springer), vol. 5, pp. 296-311, 2013.[Abstract]


Mycobacterium tuberculosis (Mtb) is a causative agent of tuberculosis (TB) disease, which has affected approximately 2 billion people worldwide. Due to the emergence of resistance towards the existing drugs, discovery of new anti-TB drugs is an important global healthcare challenge. To address this problem, there is an urgent need to identify new drug targets in Mtb. In the present study, the subtractive genomics approach has been employed for the identification of new drug targets against TB. Screening the Mtb proteome using the Database of Essential Genes (DEG) and human proteome resulted in the identification of 60 key proteins which have no eukaryotic counterparts. Critical analysis of these proteins using Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways database revealed uridine monophosphate kinase (UMPK) enzyme as a potential drug target for developing novel anti-TB drugs. Homology model of Mtb-UMPK was constructed for the first time on the basis of the crystal structure of E. coli-UMPK, in order to understand its structure-function relationships, and which would in turn facilitate to perform structure-based inhibitor design. Furthermore, the structural similarity search was carried out using physiological inhibitor UTP of Mtb-UMPK to virtually screen ZINC database. Retrieved hits were further screened by implementing several filters like ADME and toxicity followed by molecular docking. Finally, on the basis of the Glide docking score and the mode of binding, 6 putative leads were identified as inhibitors of this enzyme which can potentially emerge as future drugs for the treatment of TB. More »»

2013

Journal Article

Dr. Jayakumar Rangasamy, Mohan, J. C., G, P., and P, C. K., “Induction of in Vitro Apoptosis by Gold Nanoparticles Functionalized with Sodium Citrate and Poly(ethylene Imine) in Human Cancer Cell Lines”, Journal of Experimental Nanoscience, vol. 8, no. 1, pp. 32-45, 2013.

2013

Journal Article

B. Tian, Dr. Sahadev Shankarappa, Chang, H. H., Tong, R., and Kohane, D. S., “Biodegradable Mesostructured Polymer Membranes”, Nano Letters, vol. 13, pp. 4410-4415, 2013.[Abstract]


The extracellular matrix (ECM) has a quasi-ordered reticular mesostructure with feature sizes on the order of tenths of to a few hundred nanometers. Approaches to preparing biodegradable synthetic scaffolds for engineered tissues that have the critical mesostructure to mimic ECM are few. Here we present a simple and general solvent evaporation-induced self-assembly (EISA) approach to preparing concentrically reticular mesostructured polyol–polyester membranes. The mesostructures were formed by a novel self-assembly process without covalent or electrostatic interactions, which yielded feature sizes matching those of ECM. The mesostructured materials were nonionic, hydrophilic, and water-permeable and could be shaped into arbitrary geometries such as conformally molded tubular sacs and micropatterned meshes. Importantly, the mesostructured polymers were biodegradable and were used as ultrathin temporary substrates for engineering vascular tissue constructs.

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2013

Journal Article

Dr. Sahadev Shankarappa, B, M. A., G, R., C, S., and DS, K., “Local Toxicity from Local Anesthetic Polymeric Microparticles”, Anesthesia and Analgesia, no. 116, pp. 794-803 , 2013.

2013

Journal Article

Dr. Sahadev Shankarappa, Wang, L., R, T., JB, C., JH, T., HH, C., and DS, K., “Topical Drug Formulations for Prolonged Corneal Anesthesia”, Cornea, 2013, 2013.

2013

Journal Article

B. Mizrahi, Dr. Sahadev Shankarappa, Hickey, J. M., Dohlman, J. C., Timko, B. P., Whitehead, K. A., Lee, J. - J., Langer, R., Anderson, D. G., and Kohane, D. S., “A Stiff Injectable Biodegradable Elastomer”, Advanced Functional Materials, vol. 23, pp. 1527-1533, 2013.[Abstract]


Injectable materials often have shortcomings in mechanical and drug-eluting properties that are attributable to their high water contents. A water-free, liquid four-armed PEG modified with dopamine end groups is described which changes from liquid to elastic solid by reaction with a small volume of Fe3+ solution. The elastic modulus and degradation times increase with increasing Fe3+ concentrations. Both the free base and the water-soluble form of lidocaine can be dissolved in the PEG4-dopamine and released in a sustained manner from the cross-linked matrix. PEG4-dopamine is retained in the subcutaneous space in vivo for up to 3 weeks with minimal inflammation. This material's tailorable mechanical properties, biocompatibility, ability to incorporate hydrophilic and hydrophobic drugs and release them slowly are desirable traits for drug delivery and other biomedical applications.</p>

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2013

Journal Article

Dr. Sahadev Shankarappa and DS, K., “Can Nerve Blockade be Used to Manage Neuropathic Pain?”, Pain management, vol. 3, no. 2, pp. 91-93, 2013.

2013

Journal Article

Sowmya S, Jayakumar R., and Shantikumar V Nair, “Advantages of chitin-based nanobiomaterials in nanomedicine”, Marine Biomaterials: Characterization, Isolation and Applications, 2013.[Abstract]


The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO, 2008) have recognized a need for scientic advice on any food safety implications that may arise from the use of nanotechnologies in the food and agriculture

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2013

Journal Article

, K.V., S., G., R., Shantikumar V Nair, K.R.V, S., and V.-K., L., “Development of activated carbon-ceria nanocomposite materials for prostate cancer therapy”, Advanced Science, Engineering and Medicine, 2013.[Abstract]


Using electrophoretic co-deposition (EPD), nanocomposite of ball-milled activated carbon and cerium (IV) oxide (CeO2) (or) ceria was prepared as a thin film. Nanocomposite preparation was done and deposited on aluminium foil. Phase analyses were carried out using X-ray diffraction analysis (XRD) showing the uniform compositional profile of the composite. The elemental analysis of ceria, oxygen and carbon was carried out using X-ray photoelectron spectroscopy (XPS). Detailed scanning electron microscopy analysis showed that ball-milled activated carbon, ceria and carbon-ceria composite were formed on the nanoscale and uniformly distributed. The toxicity of activated carbon ceria nanocomposite towards the prostate cancer cell line was evaluated and found to be toxic towards prostate cancer cell lines (PC-3) as analyzed by MTT assay.

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2012

Journal Article

A. Sasidharan, Panchakarla, L. S., Sadanandan, A. R., Ashokan, A., Chandran, P., Girish, C. Madathil, Menon, D., Nair, S. V., Rao, C. N. R., and Koyakutty, M., “Hemocompatibility and macrophage response of pristine and functionalized graphene.”, Small, vol. 8, no. 8, pp. 1251-63, 2012.[Abstract]


<p>Graphene and its derivatives are being proposed for several important biomedical applications including drug delivery, gene delivery, contrast imaging, and anticancer therapy. Most of these applications demand intravenous injection of graphene and hence evaluation of its hemocompatibility is an essential prerequisite. Herein, both pristine and functionalized graphene are extensively characterized for their interactions with murine macrophage RAW 264.7 cells and human primary blood components. Detailed analyses of the potential uptake by macrophages, effects on its metabolic activity, membrane integrity, induction of reactive oxygen stress, hemolysis, platelet activation, platelet aggregation, coagulation cascade, cytokine induction, immune cell activation, and immune cell suppression are performed using optimized protocols for nanotoxicity evaluation. Electron microscopy, confocal Raman spectral mapping, and confocal fluorescence imaging studies show active interaction of both the graphene systems with macrophage cells, and the reactive oxygen species mediated toxicity effects of hydrophobic pristine samples are significantly reduced by surface functionalization. In the case of hemocompatibility, both types of graphene show excellent compatibility with red blood cells, platelets, and plasma coagulation pathways, and minimal alteration in the cytokine expression by human peripheral blood mononuclear cells. Further, both samples do not cause any premature immune cell activation or suppression up to a relatively high concentration of 75 μg mL(-1) after 72 h of incubation under in vitro conditions. This study clearly suggests that the observed toxicity effects of pristine graphene towards macrophage cells can be easily averted by surface functionalization and both the systems show excellent hemocompatibility.</p>

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2012

Journal Article

A. A. Madhavan, Kalluri, S., Arun, T. A., Nagarajan, S., Subramanian, K. R. V., A. Nair, S., Nair, S. V., and Balakrishnan, A., “Electrical and optical properties of electrospun TiO2-graphene composite nanofibers and its application as DSSC photo-anodes”, RSC Advances, vol. 2, pp. 13032-13037, 2012.[Abstract]


The present study reports the electrospinning of TiO2-graphene composite nanofibers to develop conductive nano-fiber mats using polyvinylpyrrolidone as a carrier solution. This carrier solution was sublimated at 450 °C to attain a complete conducting continuous nanofibrous network. It was observed during the annealing that as the graphene content was increased to 1 wt% the continuous fiber morphology was lost. Annealing did not have any impact on the fiber diameter (∼150 nm) or morphology as the graphene content was maintained between 0.0-0.7 wt%. The surface porosity of these samples was found be in the range of 45-48%. The presence of graphene in TiO2 nanofibers was confirmed using Raman spectroscopy. Photoluminescence spectroscopy showed excitonic intensity to be lower in graphene-TiO2 samples indicating that the recombination of photo-induced electrons and holes in TiO2 can be effectively inhibited in the composite nanofibers. Fluorescence spectroscopy was used to confirm this phenomenon where blue and quenched emissions were observed for the electrospun TiO2 nanofibers and composite fibers, respectively. Conductivity measurements showed the mean specific conductance values obtained for TiO2-graphene composites to be about two times higher values than that of the electrospun TiO2 fibers. Assembling these TiO2-graphene fiber composites as photoanodes in dye sensitized solar cells, an efficiency of 7.6% was attained. © 2012 The Royal Society of Chemistry. More »»

2012

Journal Article

D. Menon, Basanth, A., Retnakumari, A., Manzoor, K., and Nair, S. V., “Green synthesis of biocompatible gold nanocrystals with tunable surface plasmon resonance using garlic phytochemicals”, Journal of Biomedical Nanotechnology, vol. 8, pp. 901-911, 2012.[Abstract]


Synthesis of biocompatible gold nanoparticles having tunable optical absorbance finds immense use in biomedical applications such as cancer diagnosis and photothermal therapy. Hence, it is imperative to develop environment and bio-friendly green chemical processes that aid in preparing gold nanoparticles with tunable optical properties. In the present work, phytochemicals present in the medicinal herb, viz., garlic, were used to provide the dual effects of reduction of gold salts to gold nanoparticles as well as stabilization, in a single step process. The optical tunability of nanogold with respect to concentration of precursor and volume of garlic extract, processing conditions of garlic, its differing molecular weight fractions, reaction time and temperature has been demonstrated. The presence of a range of anisotropic nanogold including nanotriangles, nanorods and nanospheres as evident from TEM endows the colloid with a tunable optical absorption, specifically into the near infrared region. In vitro stability studies of the colloidal suspension in various media including saline, BSA, histidine and PBS showed that gold nanoparticles did not aggregate with time or differing pH conditions. The role of the garlic phytochemicals in providing stability against agglomeration was also substantiated by FTIR studies. Cytotoxicity studies performed using spherical and anisotropic gold nanoparticles on MCF-7 and L929 cell lines proved the biocompatibility of the material up to high doses of 500 μg/ml. The present work highlights the role of garlic phytochemicals in preparing biocompatible metallic gold nanoparticles with tunable optical properties and good in vitro stability, suggesting its potential use for molecular imaging or therapeutic nanomedicines. Copyright © 2012 American Scientific Publishers All rights reserved. More »»

2012

Journal Article

S. Kalluri, Madhavan, A. A., Bhupathi, P. A., Vani, R., Paravannoor, A., Nair, A. S., Nagarajan, S., Subramanian, K. R. V., Nair, S. V., and Balakrishnan, A., “Electrical properties of electrospun polyaniline-carbon black composite nanofibers”, Science of Advanced Materials, vol. 4, pp. 1220-1225, 2012.[Abstract]


The present study reports the electrospinning of commercially available polyaniline-carbon black composite to develop conductive nanofibrous mats using polyvinyl alcohol as a binder solution. This binder solution was sublimated at 230 °C to attain a complete conducting nanofiber network. The binder sublimation was confirmed using thermo gravimetric analysis (TGA). Ultra-violet visible spectroscopy was used to determine the refractive index values for porosity measurements. It was observed that the heat treatment reduced the fiber diameter from &nbsp;250 nm to &nbsp;160 nm and increased the porosity from 41±1.2% to 70±2%. The spatial specific conductance mapping using Scanning Electro-Chemical Microscopy showed that the presence of polyvinyl alcohol binder in polyaniline-carbon black composite could introduce percolation threshold. The heat-treated fibers showed four times increase in specific conductance values on removal of binder phase from the fiber structure. The role of nanoscaled Schottky barriers in determining conductive pathways through polymer by hopping mechanism and also along carbon black particles are also been proposed in this study. © 2012 by American Scientific Publishers.

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2012

Journal Article

P. T. S. Kumar, Lakshmanan, V. - K., Dr. Raja Biswas, Nair, S. V., and Dr. Jayakumar Rangasamy, “Synthesis and biological evaluation of chitin hydrogel/nano ZnO composite bandage as antibacterial wound dressing”, Journal of Biomedical Nanotechnology, vol. 8, pp. 891-900, 2012.[Abstract]


We developed chitin hydrogel/nano ZnO composite bandages using chitin hydrogel and ZnO nanoparticles (nZnO). The homogenized mixture of chitin hydrogel and nZnO was freeze-dried to obtain micro-porous composite bandages. The prepared nanocomposite bandages were characterized using FT-IR, XRD and SEM. In addition, blood clotting, antibacterial, swelling, cytocompatibility and cell attachment capability of the prepared nanocomposite bandages were evaluated. The nanocomposite bandages showed enhanced swelling, blood clotting and antibacterial activity. The incorporation of nZnO helped to attain antibacterial activity. Cytocompatibility studies were carried out using human dermal fibroblast (HDF) cells proved the non-toxic nature of the composite bandages. HDF cell attachment and infiltration analysis showed that the cells were attached and penetrated into the interior (250μm) of the nanocomposite bandages. These studies revealed that, this nanocomposite can be used for burn, diabetic and chronic wound defects. Copyright © 2012 American Scientific Publishers All rights reserved.

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2012

Journal Article

N. S. Binulal, Natarajan, A., Menon, D., Bhaskaran, V. K., Dr. Ullas Mony, and Nair, S. V., “Gelatin nanoparticles loaded poly(€-caprolactone) nanofibrous semi-synthetic scaffolds for bone tissue engineering”, Biomedical Materials (Bristol), vol. 7, 2012.[Abstract]


Nanofibrous semi-synthetic polymeric nanocomposite scaffolds were engineered by incorporating a maximum of 15 wt% biopolymeric gelatin nanoparticles (nGs) into the synthetic polymer poly(€-caprolactone) (PCL) prior to electrospinning. The effect of nGs in altering the physico-chemical properties, cell material interaction and biodegradability of the scaffolds was evaluated. Experimental results showed that the inherent hydrophobicity of PCL scaffolds remained unaltered even after the incorporation of hydrophilic nGs. However, breakdown of the continuous nanofibers into lengths less than 7 νm occurred within four to eight weeks in the presence of nGs in contrast with the greater than two year time frame for the degradation of PCL fibers alone that is known from the literature. In terms of cell-material interaction, human mesenchymal stem cells (hMSCs) were found to attach and spread better and faster on PCL-nG scaffolds compared to PCL scaffolds. However, there was no difference in hMSC proliferation and differentiation into osteogenic lineage between the scaffolds. These results indicate that PCL-nG nanofibrous nanocomposite scaffolds are an improvement over PCL scaffolds for bone tissue engineering applications in that the PCL-nG scaffolds provide improved cell interaction and are able to degrade and resorb more efficiently. © 2012 IOP Publishing Ltd.

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2012

Journal Article

R. Nandhini, Mini, P. A., Avinash, B., Nair, S. V., and Subramanian, K. R. V., “Supercapacitor electrodes using nanoscale activated carbon from graphite by ball milling”, Materials Letters, vol. 87, pp. 165-168, 2012.[Abstract]


In this letter, we report on the process of preparation of a high performance supercapacitor electrode using activated carbon of nanoscale size (&lt;100 nm). The activated carbon was processed by high-energy ball milling of graphite followed by activation treatments with nitric acid and sulphuric acid. The activated carbon was coated on titanium substrates using electrophoretic deposition and subjected to a post-deposition annealing treatment at 100°C. The electrophoretically deposited thin film layer has adequate porosity with ultrafine pores (pores with diameter ranging from 20 Å to 100 Å) that constitute majority of number of pores (&gt;95%) and hence maximally contribute to the surface area of the carbon for charge storage purposes. The designed supercapacitor electrode with nanoscale activated carbon not only has excellent storage capacity (specific capacitance of 1071 F g -1 and area capacitance of 0.48 F cm -2) but also good control of discharge when used as a power source. The above process used by us is a cost-effective and novel technique, which expands the application of activated carbon for high performance supercapacitor electrodes by achieving the desired performance. © 2012 Elsevier B.V.

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2012

Journal Article

G. Brunhofer, Fallarero, A., Karlsson, D., Batista-Gonzalez, A., Shinde, P., Dr. Gopi Mohan C., and Vuorela, P., “Exploration of Natural Compounds as Sources of New Bifunctional Scaffolds Targeting Cholinesterases and Beta Amyloid Aggregation: The Case of Chelerythrine”, Bioorganic and Medicinal Chemistry, vol. 20, pp. 6669-6679, 2012.[Abstract]


The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin - chelerythrine - acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs. © 2012 Elsevier Ltd. All rights reserved.

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2012

Journal Article

P. Zhu, Reddy, M. V., Wu, Y., Peng, S., Yang, S., Nair, A. S., Loh, K. P., Chowdari, B. V. R., and Ramakrishna, S., “Mesoporous SnO 2 agglomerates with hierarchical structures as an efficient dual-functional material for dye-sensitized solar cells”, Chemical Communications, vol. 48, pp. 10865-10867, 2012.[Abstract]


Mesoporous SnO 2 agglomerates with hierarchical structures and a high surface area were fabricated through a molten salt method. The SnO 2 demonstrated high photoelectric conversion efficiencies of 3.05% and 6.23% (with TiCl 4 treatment) in dye-sensitized solar cells, which are attributed to its dual functionality of providing high dye-loading and efficient light scattering. © 2012 The Royal Society of Chemistry.

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2012

Journal Article

A. P. Retnakumari, Hanumanthu, P. L., Malarvizhi, G. L., Prabhu, R., Sidharthan, N., Thampi, M. V., Menon, D., Mony, U., Krishnakumar N. Menon, Keechilat, P., Nair, S., and Dr. Manzoor K., “Rationally Designed Aberrant Kinase-Targeted Endogenous Protein Nanomedicine Against Oncogene Mutated/Amplified Refractory Chronic Myeloid Leukemia”, Molecular Pharmaceutics, vol. 9, pp. 3062-3078, 2012.[Abstract]


Deregulated protein kinases play a very critical role in tumorigenesis, metastasis, and drug resistance of cancer. Although molecularly targeted small molecule kinase inhibitors (SMI) are effective against many types of cancer, point mutations in the kinase domain impart drug resistance, a major challenge in the clinic. A classic example is chronic myeloid leukemia (CML) caused by BCR-ABL fusion protein, wherein a BCR-ABL kinase inhibitor, imatinib (IM), was highly successful in the early chronic phase of the disease, but failed in the advanced stages due to amplification of oncogene or point mutations in the drug-binding site of kinase domain. Here, by identifying critical molecular pathways responsible for the drug-resistance in refractory CML patient samples and a model cell line, we have rationally designed an endogenous protein nanomedicine targeted to both cell surface receptors and aberrantly activated secondary kinase in the oncogenic network. Molecular diagnosis revealed that, in addition to point mutations and amplification of oncogenic BCR-ABL kinase, relapsed/refractory patients exhibited significant activation of STAT5 signaling with correlative overexpression of transferrin receptors (TfR) on the cell membrane. Accordingly, we have developed a human serum albumin (HSA) based nanomedicine, loaded with STAT5 inhibitor (sorafenib), and surface conjugated the same with holo-transferrin (Tf) ligands for TfR specific delivery. This dual-targeted "transferrin conjugated albumin bound sorafenib" nanomedicine (Tf-nAlb-Soraf), prepared using aqueous nanoprecipitation method, displayed uniform spherical morphology with average size of ∼150 nm and drug encapsulation efficiency of ∼74%. TfR specific uptake and enhanced antileukemic activity of the nanomedicine was found maximum in the most drug resistant patient sample having the highest level of STAT5 and TfR expression, thereby confirming the accuracy of our rational design and potential of dual-targeting approach. The nanomedicine induced downregulation of key survival pathways such as pSTAT5 and antiapoptotic protein MCL-1 was demonstrated using immunoblotting. This study reveals that, by implementing molecular diagnosis, personalized nanomedicines can be rationally designed and nanoengineered by imparting therapeutic functionality to endogenous proteins to overcome clinically important challenges like molecular drug resistance. © 2012 American Chemical Society.

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2012

Journal Article

S. Maya, Indulekha, S., Sukhithasri, V., Smitha, K. T., Nair, S. V., Dr. Jayakumar Rangasamy, and Dr. Raja Biswas, “Efficacy of tetracycline encapsulated O-carboxymethyl chitosan nanoparticles against intracellular infections of Staphylococcus aureus”, International Journal of Biological Macromolecules, vol. 51, pp. 392-399, 2012.[Abstract]


Intracellular bacterial infections are recurrent, persistent and are difficult to treat because of poor penetration and limited availability of antibiotics within macrophages and epithelial cells. We developed biocompatible, 200. nm sized tetracycline encapsulated O-carboxymethyl chitosan nanoparticles (Tet-O-CMC Nps) via ionic gelation for its sustained delivery of Tet into cells. S. aureus binds and aggregates with Tet-O-CMC Nps increasing drug concentrations at the infection site. Tet-O-CMC Nps were sixfold more effective in killing intracellular S. aureus compared to Tet alone in HEK-293 and differentiated THP1 macrophage cells proving it to be an efficient nanomedicine to treat intracellular S. aureus infections. © 2012 Elsevier B.V.

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2012

Journal Article

R. Ranjusha, A. Nair, S., Ramakrishna, S., Anjali, P., Sujith, K., Subramanian, K. R. V., Sivakumar, N., Kim, T. N., Nair, S. V., and Balakrishnan, A., “Ultra fine MnO2 nanowire based high performance thin film rechargeable electrodes: Effect of surface morphology, electrolytes and concentrations”, Journal of Materials Chemistry, vol. 22, pp. 20465-20471, 2012.[Abstract]


The present study demonstrates a novel approach by which titanium foils coated with MnO2 nanowires can be processed into a high surface area electrode for rechargeable energy storage applications. A detailed study has been performed to elucidate how surface morphology and redox reaction behaviors underlying these electrodes impact the cyclic and capacitive behavior of the electrode. These nanowires were synthesized hydrothermally and exhibited an aspect ratio in the order of 102. BET analysis revealed that these MnO2 nanowires show a high surface area of 44 m2 g -1. From the analysis of the relevant electrochemical parameters, an intrinsic correlation between the capacitance, internal resistance and the surface morphology has been deduced and explained on the basis of relative contributions from the faradic properties of the MnO2 in different electrolytes. Depending on the type of surface morphology incorporated, these thin film nanowire electrodes exhibited specific mass capacitance value as high as 1050 F g-1 and 750 F g-1 measured from cyclic voltammetry and charge-discharge curves respectively. It has been shown that electrodes based on such nanowires can allow significant room for improvement in the cyclic stability of a hybrid supercapacitor/battery system. Further, a working model supercapacitor in cylindrical form is also shown exhibiting a capacitance of 10 F. © 2012 The Royal Society of Chemistry.

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2012

Journal Article

A. Anitha, Maya, S., Deepa, N., Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Curcumin-loaded N, O-carboxymethyl chitosan nanoparticles for cancer drug delivery”, Journal of Biomaterials Science, Polymer Edition, vol. 23, pp. 1381-1400, 2012.[Abstract]


Chitosan (CS) and its carboxymethyl derivatives are smart biopolymers that are non-toxic, biocompatible and biodegradable, and, hence, suitable for various biomedical applications, such as drug delivery, gene therapy and tissue engineering. Curcumin is a major chemotherapeutic agent with antioxidant, antiinflammatory, anti-proliferative, anticancer and antimicrobial effects. However, the potential of curcumin as a chemotherapeutic agent is limited by its hydrophobicity and poor bioavailability. In this work, we developed a nanoformulation of curcumin in a carboxymethyl chitosan (CMC) derivative, N, O -carboxymethyl chitosan (N,O-CMC). The curcumin-loaded N,O-CMC (curcumin-N,O-CMC) nanoparticles were characterized using DLS, AFM, SEM, FT-IR and XRD. DLS studies revealed nanoparticles with a mean diameter of 150 ± 30 nm. AFM and SEM confirmed that the particles have a spherical morphology within the size range of 150 ± 30 nm. Curcumin was entrapped with in N,O-CMC nanopartcles with an efficiency of 80%. The in vitro drug-release profile was studied at different pH (7.4 and 4.5) at 37°C for different incubation periods with and without lysozyme. Cytotoxicity studies using MTT assay indicated that curcumin-N,O-CMC nanoparticles showed specific toxicity towards cancer cells and non-toxicity to normal cells. Cellular uptake of curcumin-N,O-CMC nanoparticles was analyzed by fluorescence microscopy and was reconfirmed by flow cytometry. Overall, these results indicate that like previously reported curcumin loaded O-CMC nanoparticles, N, O-CMC will also be an efficient nanocarrier for delivering curcumin to cancer cells. © 2011 Koninklijke Brill NV, Leiden.

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2012

Journal Article

A. A. Madhavan, Kumar, G. G., Kalluri, S., Joseph, J., Nagarajan, S., Nair, S., Subramanian, K. R. V., and Balakrishnan, A., “Effect of embedded plasmonic au nanoparticles on photocatalysis of electrospun TiO2 nanofibers”, Journal of Nanoscience and Nanotechnology, vol. 12, pp. 7963-7967, 2012.[Abstract]


The present study demonstrates an original approach by which Au nanoparticles (∼10 nm) are embedded into TiO2 fibers via electrospinning. The photocatalytic performance of the resultant fibrous material was studied and related to the architecture and the nature of the internal interfaces in the composite. It was found that embedment of nano Au particles into the TiO2 fiber significantly improved the photocatalytic performance as compared to non-embedded ones. Electrospun fibers with the Au nanoparticles (∼10 nm) showed an average fiber diameter of ∼380 nm. The photocatalytic studies of Au embedded TiO2 fibers using ultra-violet (UV) visible spectroscopy showed ∼35% increase in photocatalytic activity when compared to the TiO2 fibers without the Au nanoparticles after 7 hrs of UV irradiation. This increase in photocatalysis was attributed to the ability of Au to increase charge separation in TiO 2 and also to the ability of Au to transfer plasmonic energy to the dye. Copyright © 2012 American Scientific Publishers. All rights reserved.

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2012

Journal Article

V. A. Ganesh, Nair, A. S., Raut, H. K., Tan, T. T. Yuan, He, C., Ramakrishna, S., and Xu, J., “Superhydrophobic fluorinated POSS-PVDF-HFP nanocomposite coating on glass by electrospinning”, Journal of Materials Chemistry, vol. 22, pp. 18479-18485, 2012.[Abstract]


Fluorinated polyhedral oligomeric silsesquioxanes-poly(vinylidene fluoride-co-hexafluoro propylene) (fluoroPOSS-PVDF-HFP) nanocomposite mixtures are prepared by individually mixing two fluorinated POSS materials (FP8 and FPSi8) with PVDF-HFP solution and transparent superhydrophobic coatings on a glass substrate are produced by electrospinning. The fabricated superhydrophobic surface exhibits continuous, uniform and non-beaded nanofibers with a high water contact angle (157.3°) and a low sliding angle (SA &lt; 5°). The superhydrophobic properties including surface energy, water contact angle, and contact angle hysteresis as well as the optical properties are studied by altering the wt% of fluoroPOSS in PVDF-HFP solution. It is observed that due to the increase in the viscosity of the solution, the diameter of the nanofibers increases with increase in the concentration of fluoroPOSS. It is also observed that as the concentration of fluoroPOSS in PVDF solution increases, the amount of fluorine content increases thereby the surface energy of the coating decreases (to around 10 mN m -1) leading to a superhydrophobic surface with low contact angle hysteresis (&lt;5°). The optical properties of the coatings produced using FPSi8 fluoroPOSS-PVDF-HFP mixture are compared with those of FP8 fluoroPOSS, and the former is found to be more transparent due to its relatively high solubility in PVDF-HFP. © 2012 The Royal Society of Chemistry.

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2012

Journal Article

Anusha Ashokan, Chandran, P., Sadanandan, A. R., Koduri, C. K., Retnakumari, A. P., Menon, D., Shantikumar V Nair, and Dr. Manzoor K., “Development and Haematotoxicological Evaluation of Doped Hydroxyapatite based Multimodal Nanocontrast Agent for Near-infrared, Magnetic Resonance and X-ray Contrast Imaging”, Nanotoxicology, vol. 6, pp. 652-666, 2012.[Abstract]


Multimodal molecular imaging provides both anatomical and molecular information, aiding early stage detection and better treatment planning of diseased conditions. Here, we report development and nanotoxicity evaluation of a novel hydroxyapatite nanoparticle (nHAp) based multimodal contrast agent for combined near-infrared (NIR), MR and X-ray imaging. Under optimised wet-chemical conditions, we achieved simultaneous doping of nHAp (size ∼50 nm) with indocyanine green and Gd3+ contributing to NIR contrast (∼750–850 nm), paramagnetic behaviour and X-ray absorption suitable for NIR, MR and X-ray contrast imaging, respectively. Haematocompatibility studies using stem cell viability, haemolysis, platelet activation, platelet aggregation and coagulation time analysis indicated excellent compatibility of doped nHAp (D-nHAp). Further, the immunogenic function studies using human lymphocytes (in vitro) showed that D-nHAp caused no adverse effects. Collectively, our studies suggest that D-nHAp with excellent biocompatibility and multifunctional properties is a promising nanocontrast agent for combined NIR, MR and X-ray imaging applications

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2012

Journal Article

Aad Arvind, Kumar, Va, Saravanan, Pb, and Dr. Gopi Mohan C., “Homology modeling, molecular dynamics and inhibitor binding study on MurD ligase of Mycobacterium tuberculosis”, Interdisciplinary Sciences: Computational Life Sciences, vol. 4, pp. 223-238, 2012.[Abstract]


The cell wall of mycobacterium offers well validated targets which can be exploited for discovery of new lead compounds. MurC-MurF ligases catalyze a series of irreversible steps in the biosynthesis of peptidoglycan precursor, i.e. MurD catalyzes the ligation of D-glutamate to the nucleotide precursor UMA. The three dimensional structure of Mtb-MurD is not known and was predicted by us for the first time using comparative homology modeling technique. The accuracy and stability of the predicted Mtb-MurD structure was validated using Procheck and molecular dynamics simulation. Key interactions in Mtb-MurD were studied using docking analysis of available transition state inhibitors of E.coli-MurD. The docking analysis revealed that analogues of both L and D forms of glutamic acid have similar interaction profiles with Mtb-MurD. Further, residues His192, Arg382, Ser463, and Tyr470 are proposed to be important for inhibitor-(Mtb-MurD) interactions. We also identified few pharmacophoric features essential for Mtb-MurD ligase inhibitory activity and which can further been utilized for the discovery of putative antitubercular chemotherapy. © 2012 International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg.

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2012

Journal Article

N. Ganesh, Dr. Jayakumar Rangasamy, Koyakutty, M., Dr. Ullas Mony, and Nair, S. V., “Embedded silica nanoparticles in poly(caprolactone) nanofibrous scaffolds enhanced osteogenic potential for bone tissue engineering”, Tissue Engineering - Part A, vol. 18, pp. 1867-1881, 2012.[Abstract]


Poly(caprolactone) (PCL) has been frequently considered for bone tissue engineering because of its excellent biocompatibility. A drawback, however, of PCL is its inadequate mechanical strength for bone tissue engineering and its inadequate bioactivity to promote bone tissue regeneration from mesenchymal stem cells. To correct this deficiency, this work investigates the addition of nanoparticles of silica (nSiO2) to the scaffold to take advantage of the known bioactivity of silica as an osteogenic material and also to improve the mechanical properties through nanoscale reinforcement of the PCL fibers. The nanocomposite scaffolds and the pristine PCL scaffolds were evaluated physicochemically, mechanically, and biologically in the presence of human mesenchymal stem cells (hMSCs). The results indicated that, when the nanoparticles of size approximately 10 nm (concentrations of 0.5% and 1% w/v) were embedded within, or attached to, the PCL nanofibers, there was a substantial increase in scaffold strength, protein adsorption, and osteogenic differentiation of hMSCs. These nSiO2 nanoparticles, when directly added to the cells evidently pointed to ingestion of these particles by the cells followed by cell death. The polymer nanofibers appeared to protect the cells by preventing ingestion of the silica nanoparticles, while at the same time adequately exposing them on fiber surfaces for their desired bioactivity. © Copyright 2012, Mary Ann Liebert, Inc.

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2012

Journal Article

D. Sankar, Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “Fabrication of chitin/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) hydrogel scaffold”, Carbohydrate Polymers, vol. 90, pp. 725-729, 2012.[Abstract]


Regeneration of skin after a large area wound or burn is often difficult without the aid of a scaffold. In this work we developed a 3D macroporous chitin/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hydrogel blend by normal solution chemistry and lyophilized it to get the scaffold. The developed scaffold was then characterized and it showed a slow degrading as well as biocompatible nature. The blend hydrogel scaffold showed 67% porosity and the pore size was less than 20 μm. Cytocompatibility of the scaffold was proved by Alamar blue assay using Human Dermal Fibroblast cells (HDF). The blend hydrogel scaffold showed a two fold increase in cell number over control within three days of culture. The chitin/PHBV blend also showed enhanced HDF cell attachment and proliferation. These preliminary results prove its suitability for scaffold based skin tissue regeneration. © 2012 Elsevier Ltd.

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2012

Journal Article

Aab Pandey, P, Jab, Tripathi, S., and Dr. Gopi Mohan C., “Harnessing human N-type Ca2+ channel receptor by identifying the atomic hotspot regions for its structure-based blocker design”, Molecular Informatics, vol. 31, pp. 643-657, 2012.[Abstract]


<p>The voltage dependent N-type Ca2+ channel (NCC) receptor was identified to have therapeutic potential for the treatment of neuropathic pain and stroke disease. The Ca2+ ion transport through the transmembrane influx is mainly dependent on the closing, opening, or intermediate state gating mechanism of NCC. Harnessing this dynamic gating mechanism at the structural level is an important and challenging physiological phenomenon. The three dimensional (3D) structure of this membrane receptor is not yet experimentally determined to understand its mechanism of action. Based on these observations, we have developed for the first time the structure of the closed state of the NCC receptor at the pore forming domains which mainly involve three transmembrane helices (TMhs) S5, P and S6. Hot-spot binding site residues of this receptor model were identified by molecular docking technique using amlodipine, cilnidipine and nifedipine compounds known to be potent Ca 2+ channel antagonists. Further, the Ca2+ ion permeability and the hydrophobic gating mechanism provided better structural and functional insights on the NCC receptor. These results are in consonance with other Ca 2+ channel receptors and would provide guidance for further biochemical investigations. Copyright © 2012 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.</p>

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2012

Journal Article

Da Karlsson, Fallarero, Aa, Brunhofer, Gab, Mayer, Cb, Prakash, Oc, Dr. Gopi Mohan C., Vuorela, Pa, and Erker, Tb, “The exploration of thienothiazines as selective butyrylcholinesterase inhibitors”, European Journal of Pharmaceutical Sciences, vol. 47, pp. 190-205, 2012.[Abstract]


The role of butyrylcholinesterase (BChE) in the progression of Alzheimer's disease (AD) has recently become more crucial. In the AD brain, selective BChE inhibitors have been demonstrated to have a beneficial effect in vivo, probably by recovering cholinergic activity and/or by restoring AChE:BChE activity ratios to the levels observed in the healthy brain. Thienothiazines are compounds sharing some structural features with phenothiazines, which are known to be potent BChE inhibitors. Thus, in this contribution 45 thienothiazines were investigated for their BChE inhibitory activity. Six of them were proven to be potent and selective inhibitors of equine BChE's hydrolase activity. Structure-activity relationships were laid out, and a tentative pharmacophore model for BChE inhibitors of the thienothiazine type was proposed. The most active compound, 3f, displayed a mixed type of inhibition and was also active against the human BChE (huBChE) with an IC50 huBChE of 0.51 ± 0.07 μM. Computational studies suggested that 3f likely binds to the catalytic site and nearby to the peripheral site of the huBChE in an extended form. In addition, the chemical space occupied by the active thienothiazines, as opposed to phenothiazines and other representative chemical classes of BChE inhibitors, was explored with the aid of ChemGPS-NP, and the relevant chemical space regions were identified. This study shows for the first time that thienothiazines represent a new group of BChE inhibitors that can be used as molecular probes for studying the role of BChE in the brain or for developing newer drug leads for AD therapy. © 2012 Elsevier B.V. All rights reserved.

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2012

Journal Article

S. V. Nair, Balakrishnan, A., Subramanian, K. R. V., Manu, A., Asha, A. M., and Deepika, B., “Effect of TiO 2 nanotube length and lateral tubular spacing on photovoltaic properties of back illuminated dye sensitized solar cell”, Bulletin of Materials Science, vol. 35, pp. 489-493, 2012.[Abstract]


The main objective of this study is to show the effect of TiO 2 nanotube length, diameter and intertubular lateral spacings on the performance of back illuminated dye sensitized solar cells (DSSCs). The present study shows that processing short TiO 2 nanotubes with good lateral spacings could significantly improve the performance of back illuminated DSSCs. Vertically aligned, uniform sized diameter TiO 2 nanotube arrays of different tube lengths have been fabricated on Ti plates by a controlled anodization technique at different times of 24, 36, 48 and 72 h using ethylene glycol and ammonium fluoride as an electrolyte medium. Scanning electron microscopy (SEM) showed formation of nanotube arrays spread uniformly over a large area. X-ray diffraction (XRD) of TiO 2 nanotube layer revealed the presence of crystalline anatase phases. By employing the TiO 2 nanotube array anodized at 24 h showing a diameter ̃80 nm and length ̃1·5 μm as the photo-anode for back illuminated DSSCs, a full-sun conversion efficiency (η) of 3·5%was achieved, the highest value reported for this length of nanotubes. © Indian Academy of Sciences.

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2012

Journal Article

R. Ranjusha, Sreeja, R., Mini, P. A., Subramanian, K. R. V., Nair, S. V., and Balakrishnan, A., “Electrical and optical characteristics of surface treated ZnO nanotubes”, Materials Research Bulletin, vol. 47, pp. 1887-1891, 2012.[Abstract]


Vertical ZnO nanotubes were electrochemically deposited onto an indium doped tin oxide glass substrate. These nanotubes were surface treated with zinc acetate and annealed at 450°C, resulting in a nanotubes/nanoparticles composite layer. Scanning electron microscopy of the surface treated samples showed nanoparticles been dispersed uniformly along the ZnO tubular matrix, which was confirmed by X-ray diffractrometry. Photoluminescence and fluorescence microscopy showed untreated ZnO nanotubes exhibiting blue emission, while the treated samples exhibited green emissions. Ultra-violet spectroscopy of treated samples revealed lower band gap values compare to their untreated counterparts. Lifetime measurements showed higher excitonic lifetimes in treated samples. Conductance studies using atomic force microscopy showed significant improvement in the conductance values for the treated samples. A significant increase in photocurrent was observed in treated samples when used as photo-anodes in dye sensitized solar cells. © 2012 Elsevier Ltd. All rights reserved.

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2012

Journal Article

A. A. Madhavan, Kalluri, S., Paravannoor, A., Nagarajan, S., Subramanian, K. R. V., Nair, S., and Balakrishnan, A., “Effect of surface nanomorphology and interfacial galvanic coupling of pedot-titanium counter electrodes on the stability of dye-Sensitized Solar Cell”, Journal of Nanoscience and Nanotechnology, vol. 12, pp. 6340-6345, 2012.[Abstract]


The present study demonstrates a novel approach by which titanium foils coated with electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT) in combination with sputtered platinum can be processed into a high-surface area cathodes for dye-sensitized solar cells (DSSCs). A detailed study has been performed to elucidate how surface nanomorphology and I-/I3- redox reaction behaviors underlying these photocathodes impact the DSSC performances. From the analysis of the relevant electrochemical parameters, an intrinsic correlation between the photovoltaic performances and the cathode surface area has been deduced for such a system and explained on the basis of relative contributions of the galvanic coupling properties of the nanomorphology PEDOT film and platinum. Depending on the type of photocathodes incorporated, it was observed that these PEDOT coated cathodes can exhibit higher stability over a given time range and photo-conversion efficiencies 12-40%, higher than that achievable in absence of the intermediate PEDOT coatings. It has been shown that DSSCs based on such metal-polymer hybrid photo-cathodes allow significant room for improvement in the catalytic performance at the electrode/electrolyte interface. Copyright © 2012 American Scientific Publishers.

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2012

Journal Article

P. A. Mini, Sherine, A., Shalumon, K. T., Balakrishnan, A., Nair, S. V., and Subramanian, K. R. V., “Current voltage analysis and band diagram of Ti/TiO 2 nanotubes Schottky junction”, Applied Physics A: Materials Science and Processing, vol. 108, pp. 393-400, 2012.[Abstract]


Here, we report on how the energy band diagram of a nanostructured semiconductor- metal interface aligns in accordance with semiconductor morphology. Electrochemically, titanium metal is anodized to form titanium dioxide nanotubes, which forms a junction with the free Ti substrate and this junction forms a natural Schottky barrier. With reduced dimensionality of the nanotube structures (lower wall thickness), we have observed band edge movements and band gap quantum confinement effects and lowering of the Schottky barrier. These results were corroborated with the help of cyclic voltammetry, ultraviolet-visible spectrometry, and impedance analysis. Current voltage analysis of the Schottky barrier showed a lowering of the barrier (by 25 %) with reducing dimensionality of the nanotube structures. At externally applied voltages higher than the Schottky barrier, charges can travel along the nanotubes and reside at an interface between the nanotubes and a high-? dielectric. This property was utilized to develop high surface area solid-state capacitors. © Springer-Verlag 2012.

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2012

Journal Article

K. Pa Sanosh, Kim, T. Na, and Balakrishnan, Ab, “Mechanical properties of pressure-less sintered zirconia-magnesium aluminum silicate glass composite”, Journal of Composite Materials, vol. 46, pp. 1739-1743, 2012.[Abstract]


The main objective of the present study was to develop a high-strength machinable ceramic based on zirconia (ZrO 2) and magnesium aluminum silicate (Mg 3Al 2Si 6O 18; MAS) glass system through pressure-less sintering. Pressure-less sintering of ZrO 2, 3 mol% yttria-stabilized (YSZ) was carried out at 1450°C in air, using 10 wt% MAS glass as a sintering additive. The influence of glass on the microstructure and mechanical properties of the composite was investigated. The presence of glass into the ZrO 2 matrix was substantiated using scanning electron microscopy (SEM). X-ray diffractometry (XRD) revealed no crystalline phases other than tetragonal ZrO 2. The flexural strength of the composite was found to be ∼30% higher than YSZ. The apparent crack resistance was determined by Vickers microindentations carried out at different loads ranging from 9.8 to 196 N. The apparent crack length on the surface at each load was found to be decreased (6-21%) in YSZ and the corresponding crack-resistance values increased by about 5-20%. Both YSZ and composite showed rising trend in crack-resistance values as the indentation load was increased. Improved properties of composite sample were attributed to the formation of a relatively larger process zone surrounding the crack, crack-arrest behavior due to the localized compressive stresses, and the crack-bridging phenomena. © The Author(s) 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions. nav.

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2012

Journal Article

G. Nitya, Nair, G. T., Dr. Ullas Mony, Chennazhi, K. P., and Nair, S. V., “In vitro evaluation of electrospun PCL/nanoclay composite scaffold for bone tissue engineering”, Journal of Materials Science: Materials in Medicine, vol. 23, pp. 1749-1761, 2012.[Abstract]


Polycaprolactone (PCL) is a widely accepted synthetic biodegradable polymer for tissue engineering, however its use in hard tissue engineering is limited because of its inadequate mechanical strength and low bioactivity. In this study, we used halloysite nanoclay (NC) as an inorganic filler material to prepare PCL/NC fibrous scaffolds via electrospinning technique after intercalating NC within PCL by solution intercalation method. The obtained nanofibrous mat was found to be mechanically superior to PCL fibrous scaffolds. These scaffolds allowed greater protein adsorption and enhanced mineralization when incubated in simulated body fluid. Moreover, our results indicated that human mesenchymal stem cells (hMSCs) seeded on these scaffolds were viable and could proliferate faster than in PCL scaffolds as confirmed by fluorescence and scanning electron microscopic observations. Further, osteogenic differentiation of hMSCs on nanoclay embedded scaffolds was demonstrated by an increase in alkaline phosphatase activity when compared to PCL scaffold without nanoclay. All of these results suggest the potential of PCL/NC scaffolds for bone tissue engineering. © Springer Science+Business Media, LLC 2012.

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2012

Journal Article

K. S. Snima, Dr. Jayakumar Rangasamy, Unnikrishnan, A. G., Nair, S. V., and Lakshmanan, V. K., “O-Carboxymethyl Chitosan Nanoparticles for Metformin Delivery to Pancreatic Cancer Cells”, Carbohydrate Polymers, vol. 89, pp. 1003-1007, 2012.[Abstract]


In this work we developed metformin loaded O-carboxymethyl chitosan (O-CMC) nanoparticles (NPs) by ionic-gelation method. The prepared NPs of 240 ± 50 nm size with spherical morphology exhibited a pH sensitive release of metformin in vitro. Cytotoxicity studies showed that the drug-incorporated NPs induced significant toxicity on pancreatic cancer cells (MiaPaCa-2) compared to normal cells (L929). Metformin loaded NPs exhibited nonspecific internalization by normal and pancreatic cancer cells; however metformin released from the NPs induced preferential toxicity on pancreatic cancer cells. Our preliminary studies suggested that such a novel approach could possibly overcome the current limitations of metformin in its clinical application against pancreatic cancer. © 2012 Elsevier Ltd. All rights reserved.

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2012

Journal Article

S. Parvathy, Ranjusha, R., Sujith, K., Subramanian, K. R. V., Sivakumar, N., Nair, S. V., and Balakrishnan, A., “Cycling performance of nanocrystalline LiMn 2O 4 thin films via electrophoresis”, Journal of Nanomaterials, vol. 2012, 2012.[Abstract]


The present study demonstrates a novel approach by which titanium foils coated with LiMn 2O 4 nanocrystals can be processed into a high-surface-area electrode for rechargeable batteries. A detailed study has been performed to elucidate how surface morphology and redox reaction behaviors underlying these electrodes impact the cyclic and capacity behavior. These nanocrystals were synthesized by in situ sintering and exhibited a uniform size of ∼55nm. A direct deposition technique based on electrophoresis is employed to coat LiMn 2O 4 nanocrystals onto titanium substrates. From the analysis of the relevant electrochemical parameters, an intrinsic correlation between the cyclability and particle size has been deduced and explained in accordance with the Li intercalation/deintercalation process. Depending on the particle size incorporated on these electrodes, it is seen that in terms of capacitance fading, for nanoparticles cyclability is better than their micron-sized counterparts. It has been shown that electrodes based on such nanocrystalline thin film system can allow significant room for improvement in the cyclic performance at the electrode/electrolyte interface. © 2012 S. Parvathy et al.

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2012

Journal Article

K. T. Shalumon, Sathish, D., Nair, S. V., Chennazhi, K. P., Tamura, H., and Dr. Jayakumar Rangasamy, “Fabrication of aligned poly (lactic acid)-chitosan nanofibers by novel parallel blade collector method for skin tissue engineering”, Journal of biomedical nanotechnology, vol. 8, pp. 405–416, 2012.[Abstract]


Poly(lactic acid) (PLA) was blended with chitosan (CS) to fabricate electrospun aligned PLA-CS nanofibers. These prepared nanofibers were aligned using a novel collector made of parallel blades which is designed to increase the transversal electric field across the gap. SEM images show that the fiber diameter mostly ranges between 150±60 nm and Fourier Transform Infrared Spectroscopy (FTIR) analysis confirm the presence of PLA and CS. X-Ray Diffraction (XRD) studies explains the amorphous nature of electrospun PLA-CS nanofibers, suitable for faster degradation. Degradation studies confirmed that PLA-CS nanofiber has enhanced degradation than the pure PLA fibers. Cell studies with human dermal fibroblasts (HDF) show the orientation of cells along the direction of fiber alignment. The results indicate that the prepared PLA-CS aligned nanofibers are promising material for skin tissue engineering.

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2012

Journal Article

A. T. Kunnath, Madhusoodanan, A., and Dr. Maneesha V. Ramesh, “Locating emergency responders in disaster area using wireless sensor network”, Lecture Notes of the Institute for Computer Sciences, Social-Informatics and Telecommunications Engineering, vol. 72 LNICST, pp. 1-10, 2012.[Abstract]


A worldwide increase in number of natural hazards is causing heavy loss of human life and infrastructure. An effective disaster management system is required to reduce the impacts of natural hazards on common life. The first hand responders play a major role in effective and efficient disaster management. Locating and tracking the first hand responders are necessary to organize and manage real-time delivery of medical and food supplies for disaster hit people. This requires effective communication and information processing between various groups of emergency responders in harsh and remote environments. Locating, tracking, and communicating with emergency responders can be achieved by devising a body sensor system for the emergency responders. In phase 1 of this research work, we have developed an enhanced trilateration algorithm for static and mobile wireless sensor nodes. This work discusses an algorithm and its implementation for localization of emergency responders in a disaster hit area. The indoor and outdoor experimentation results are also presented. © 2012 ICST Institute for Computer Science, Social Informatics and Telecommunications Engineering.

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2012

Journal Article

G. Renu, V.V., D. Rani, Nair, S. V., Subramanian, K. R. V., and Lakshmanan, V. - K., “Development of cerium oxide nanoparticles and its cytotoxicity in prostate cancer cells”, Advanced Science Letters, vol. 6, pp. 17-25, 2012.[Abstract]


Cerium oxide nanoparticles were synthesized by hydrothermal and hydrolysis methods. Cerous (4 +)oxide nanoparticles was produced by hydrothermal method and ceric (3 +) oxide nanoparticles were produced by hydrolysis method. The different synthesis routes adopted helped in synthesizing nanoparticles of similar size but exhibiting different properties. Detailed characterization of the nanoparticles proved that the synthesized cerium oxide nanoparticles were different in their stoichiometry. The selective toxicity of cerium oxide towards the normal and the cancer cell lines was evaluated. The nanoparticles were found to be nontoxic towards normal cell lines (L929) but cytotoxic towards prostate cancer cell lines (PC-3) as analyzed by MTT assay. Cellular uptake was confirmed by the conjugation of cerium oxide nanoparticle with a fluorescent dye rhodamine- 123 followed by optical detection of the uptake. © 2012 American Scientific Publishers All rights reserved.

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2012

Journal Article

A. Anitha, Chennazhi, K. P., Nair, S. V., and Dr. Jayakumar Rangasamy, “5-Flourouracil loaded N,O-carboxymethyl chitosan nanoparticles as an anticancer nanomedicine for breast cancer”, Journal of Biomedical Nanotechnology, vol. 8, pp. 29-42, 2012.[Abstract]


Chitosan and its carboxymethyl derivatives are smart biopolymers that are non-toxic, biocompatible, biodegradable and hence found applications in biomedical field. In the current work, we have developed 5-fluorouracil (5-FU) loaded N,O-carboxymethyl chitosan (N,O-CMC) nanoparticles (mean diameter: 80±20 nm, zeta potential: +52±47±2 mV) for cancer drug delivery. Drug entrapment efficiency (65%) and in vitro drug release studies were carried out spectrophotometricaly. Cellular internalization of the drug loaded nanoparticles was confirmed by fluorescent microscopy and flow cytometric analysis. Results of anticancer activity via MTT, apoptosis and caspase 3 assays showed the toxicity of the drug loaded nanoparticles towards breast cancer cells. As a whole these results indicates the potential of 5-FU loaded N,O-CMC nanoparticles in breast cancer chemotherapy in which the side effects of conventional chemo treatment could be reduced. Furthermore, the results of in vitro hemolytic assay and coagulation assay substantiate the blood compatibility of the system as well. Copyright © 2012 American Scientific Publishers All rights reserved.

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2012

Journal Article

K. C. Kavya, Dixit, R., Dr. Jayakumar Rangasamy, Nair, S. V., and Chennazhi, K. P., “Synthesis and characterization of chitosan/chondroitin sulfate/nano- SiO 2 composite scaffold for bone tissue engineering”, Journal of Biomedical Nanotechnology, vol. 8, pp. 149-160, 2012.[Abstract]


Chitosan, a natural polymer, is a biomaterial which is known to be osteoconductive but lacking in mechanical strength. In this work, to further enhance the mechanical property and biocompatibility of chitosan, we combined it with both chondroitin sulfate, a natural glycosaminoglycan found in bone, and nano-SiO 2. The composite scaffold of chitosan/chondroitin sulfate/nano-SiO 2 was fabricated by lyophilization. The nanocomposite scaffold showed enhanced porosity, degradation, mechanical integrity, biomineralization and protein adsorption. Biocompatibility and cell attachment-proliferation studies performed using MG-63 cells, advocate its better performance in vitro. To improve the cell seeding efficiency, we coated the scaffold surface with fibrin, which enhanced the initial cell attachment. The cumulative results suggest this novel nanocomposite scaffold to be a suitable candidate for bone tissue engineering. Copyright © 2012 American Scientific Publishers All rights reserved.

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2012

Journal Article

D. Narayanan, Anitha, A., Dr. Jayakumar Rangasamy, Nair, S. V., and Chennazhi, K. P., “Synthesis, characterization and preliminary in vitro evaluation of PTH 1-34 loaded chitosan nanoparticles for osteoporosis”, Journal of Biomedical Nanotechnology, vol. 8, pp. 98-106, 2012.[Abstract]


Human Parathyroid hormone 1-34 (PTH1-34) loaded chitosan nanoparticles (PTH 1-34 chitosan nanoparticles) via simple ionic gelation technique were prepared which can improve the bioavailability and half-life of the peptide. Chitosan nanoparticles and PTH 1-34 chitosan nanoparticles were synthesised and characterized by DLS, SEM, AFM, FT-IR and TG/DTA. Chitosan nanoparticles (40-60 nm) and PTH 1-34 chitosan nanoparticles (60-80 nm) with zeta potential of +60 and +40 mV respectively were subjected to haemolysis assay and tested for agglomeration in blood. MTT and LDH was performed assay using Saos-2, UMR 106, L929, NIH3T3. The in vitro peptide release profile at pH 7.5 for 144 h was quantified using PTH 1-34 ELISA Kit. Effect of released PTH 1-34 on Saos-2 was determined with ALP and BCA assay. These preliminary results pave way for the prospective use of such a carrier for the delivery of PTH 1-34 by multiple routes for the benefit of patients undergoing treatment for osteoporosis. Copyright © 2012 American Scientific Publishers All rights reserved.

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2012

Journal Article

P. T. Sudheesh Kumar, Lakshmanan, V. - K., Anilkumar, T. V., Ramya, C., Reshmi, P., Unnikrishnan, A. G., Nair, S. V., and Dr. Jayakumar Rangasamy, “Flexible and Microporous Chitosan Hydrogel/nano ZnO Composite Bandages for Wound Dressing: In Vitro and in Vivo Evaluation”, ACS Applied Materials and Interfaces, vol. 4, pp. 2618-2629, 2012.[Abstract]


Current wound dressings have disadvantages such as less flexibility, poor mechanical strength, lack of porosity, and a tendency for dressings to adhere onto the wound surface; in addition, a majority of the dressings did not possess antibacterial activity. Hydrogel-based wound dressings would be helpful to provide a cooling sensation and a moisture environment, as well as act as a barrier to microbes. To overcome these hassles, we have developed flexible and microporous chitosan hydrogel/nano zinc oxide composite bandages (CZBs) via the incorporation of zinc oxide nanoparticles (nZnO) into chitosan hydrogel. The prepared nanocomposite bandages were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). In addition, swelling, degradation, blood clotting, antibacterial, cytocompatibility, cell attachment on the material, and cell infiltration into the composite bandages were evaluated. The nanocomposite bandage showed enhanced swelling, blood clotting, and antibacterial activity. Cytocompatibility of the composite bandage has been analyzed in normal human dermal fibroblast cells. Cell attachment and infiltration studies showed that the cells were found attached to the nanocomposite bandages and penetrated into the interior. Furthermore, the in vivo evaluations in SpragueDawley rats revealed that these nanocomposite bandages enhanced the wound healing and helped for faster re-epithelialization and collagen deposition. The obtained data strongly encourage the use of these composite bandages for burn wounds, chronic wounds, and diabetic foot ulcers. © 2012 American Chemical Society.

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2012

Journal Article

V. V. Divya Rani, Vinoth-Kumar, L., Anitha, V. C., Manzoor, K., Deepthy, M., and Shantikumar, V. N., “Osteointegration of titanium implant is sensitive to specific nanostructure morphology”, Acta Biomaterialia, vol. 8, pp. 1976-1989, 2012.[Abstract]


An important aspect of orthopedic implant integration is the enhancement of functional activity of osteoblasts at the tissue-implant interface without any fibrous tissue intervention. Nanostructured implant surfaces are known to enhance osteoblast activity. Previously, we have reported a simple hydrothermal method for the fabrication of non-periodic nanostructures (nanoscaffold, nanoleaves and nanoneedles) on titanium implants showing good biocompatibility and a distinct osteoblast response in vitro in terms of osteoblast adhesion to the surface. In the present work, these nanostructures have been evaluated for their detailed in vitro cellular response as well as in vivo osteointegration. Our studies showed that a specific surface nanomorphology, viz. nanoleaves, which is a network of vertically aligned, non-periodic, leaf-like structures with thickness in the nanoscale, provided a distinct increase in osteoblast cell proliferation, alkaline phosphatase (ALP) activity and collagen synthesis compared to several other types of nanomorphology, such as nanotubes, nanoscaffold and nanoneedles (rods). Gene expression analysis of ALP, osteocalcin, collagen, decorin and Runx2 showed ∼20- to 40-fold up-regulation on the leaf-like topography. Cytoskeletal arrangement studies on this substrate again revealed a unique response with favorable intracellular protein expressions of vinculin, FAK and src. In vivo osteointegration study over 12 weeks on rat model (Sprague-Dawley) showed early-stage bone formation (60% bone contact by week 2 and ∼85% by week 8, p < 0.01) in the leaf-like nanopattern, without any inflammatory cytokine production. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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2012

Journal Article

Ra Saravanan, Santhi, Ka, Sivakumar, Nb, Narayanan, Vc, and Stephen, Aa, “Synthesis and characterization of ZnO and Ni doped ZnO nanorods by thermal decomposition method for spintronics application”, Materials Characterization, vol. 67, pp. 10-16, 2012.[Abstract]


Zinc oxide nanorods and diluted magnetic semiconducting Ni doped ZnO nanorods were prepared by thermal decomposition method. This method is simple and cost effective. The decomposition temperature of acetate and formation of oxide were determined by TGA before the actual synthesis process. The X-ray diffraction result indicates the single phase hexagonal structure of zinc oxide. The transmission electron microscopy and scanning electron microscopy images show rod like structure of ZnO and Ni doped ZnO samples with the diameter   35 nm and the length in few micrometers. The surface analysis was performed using X-ray photoelectron spectroscopic studies. The Ni doped ZnO exhibits room temperature ferromagnetism. This diluted magnetic semiconducting Ni doped ZnO nanorods finds its application in spintronics. © 2012 Elsevier Inc. All rights reserved.

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2012

Journal Article

Aa Sasidharan, Panchakarla, L. Sb, Sadanandan, A. Ra, Ashokan, Aa, Chandran, Pa, Girish, C. Ma, Menon, Da, Shantikumar V. Nair, Rao, C. N. Rb, and Dr. Manzoor K., “Hemocompatibility and macrophage response of pristine and functionalized graphene”, Small, vol. 8, pp. 1251-1263, 2012.[Abstract]


Graphene and its derivatives are being proposed for several important biomedical applications including drug delivery, gene delivery, contrast imaging, and anticancer therapy. Most of these applications demand intravenous injection of graphene and hence evaluation of its hemocompatibility is an essential prerequisite. Herein, both pristine and functionalized graphene are extensively characterized for their interactions with murine macrophage RAW 264.7 cells and human primary blood components. Detailed analyses of the potential uptake by macrophages, effects on its metabolic activity, membrane integrity, induction of reactive oxygen stress, hemolysis, platelet activation, platelet aggregation, coagulation cascade, cytokine induction, immune cell activation, and immune cell suppression are performed using optimized protocols for nanotoxicity evaluation. Electron microscopy, confocal Raman spectral mapping, and confocal fluorescence imaging studies show active interaction of both the graphene systems with macrophage cells, and the reactive oxygen species mediated toxicity effects of hydrophobic pristine samples are significantly reduced by surface functionalization. In the case of hemocompatibility, both types of graphene show excellent compatibility with red blood cells, platelets, and plasma coagulation pathways, and minimal alteration in the cytokine expression by human peripheral blood mononuclear cells. Further, both samples do not cause any premature immune cell activation or suppression up to a relatively high concentration of 75 μg mL -1 after 72 h of incubation under in vitro conditions. This study clearly suggests that the observed toxicity effects of pristine graphene towards macrophage cells can be easily averted by surface functionalization and both the systems show excellent hemocompatibility. Surface functionalization reduces the toxicity of pristine graphene towards macrophage cells in vitro. Macrophages show relatively high intracellular uptake of functionalized, hydrophilic graphene compared to hydrophobic pristine graphene. The excellent compatibility of both types of graphene with human blood components is demonstrated. Copyright © 2012 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.

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2012

Journal Article

D. Rani, Somasundaram, V. H., Nair, S., and Koyakutty, M., “Advances in cancer nanomedicine”, Journal of the Indian Institute of Science, vol. 92, pp. 187-218, 2012.[Abstract]


Scientific advances have significantly improved the basic understanding of biology of cancer. Now it is clear that a series of genetic alterations leading to abnormal cell division, loss of growth control and the capability to develop their own blood supply resulted in this complex scenario of cancer. Due to the lack of drug availability,adverse side effects and drug resistance, the conventional therapy failed to achieve proper treatment. During the past few years, nanomedicine has showed considerable progress in improving the cancer treatment and this review highlighted some of the recent advancement in this field of research. Development of first generation nanomedicine such as cytotoxic drug loaded polymeric nanoparticles, micelles, liposomes, dendrimers, carbon nanostructures, inorganic nanoparticles, etc were discussed in detail. A detailed understanding of the mechanism of cancer leading to the evolution of second generation of nanomedicine aids more efficient targeted cancer therapy. Nanoparticle mediated magnetic hyperthermia, photothermal therapy and radiofrequency hyperthermia is also reviewed as new generation cancer nanotherapeutics. © Indian Institute of Science.

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2012

Journal Article

V. G. Deepagan, Sarmento, B., Menon, D., Nascimento, A., Jayasree, A., Sreeranganathan, M., Dr. Manzoor K., Nair, S. V., and Dr. Jayakumar Rangasamy, “In Vitro Targeted Imaging and Delivery of Camptothecin using Cetuximab-Conjugated Multifunctional PLGA-ZnS Nanoparticles”, Nanomedicine, vol. 7, pp. 507-519, 2012.[Abstract]


Background: Targeted cancer therapy has been extensively developed to improve the quality of treatment by reducing the systemic exposure of cytotoxic drug. Polymeric nanoparticles with conjugated targeting agents are widely investigated because they offer tunability in particle size, drug release profile and biocompatibility. Materials &amp; methods: Here, we have prepared targeted multifunctional nanoparticles composed of a poly(lactic-co-glycolic acid) matrix, ZnS:Mn 2+ quantum dots and camptothecin, and targeted them to EGF receptor overexpressing cells with a cetuximab antibody. Results: Physicochemical characterization of multifunctional nanoparticles showed stable particles with sizes of &lt;200 nm. In vitro drug release and blood contact studies showed a sustained release profile, with limited hemolysis. In vitro cytotoxicity and cell uptake studies were carried out in A549, KB and MFC-7 cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, FACS, fluorescent microscopic images and spectroflourimetry. Conclusion: Our studies revealed higher camptothecin activity and uptake in cell lines that overexpress the EGF receptor. All these results suggest that anti-EGF receptor cetuximab-conjugated poly(lactic-co-glycolic acid) multifunctional nanoparticles can be used as a potential nanomedicine against cancer. © 2012 Future Medicine Ltd.

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2012

Journal Article

G. Praveen, Sreerekha, P. R., Menon, D., Nair, S. V., and Chennazhi, K. P., “Fibrin nanoconstructs: A novel processing method and their use as controlled delivery agents”, Nanotechnology, vol. 23, 2012.[Abstract]


Fibrin nanoconstructs (FNCs) were prepared through a modified water-in-oil emulsificationdiffusion route without the use of any surfactants, resulting in a high yield synthesis of fibrin nanotubes (FNTs) and fibrin nanoparticles (FNPs). The fibrin nanoconstructs formed an aligned structure with self-assembled nanotubes with closed heads that eventually formed spherical nanoparticles of size ∼250nm. The nanotubes were typically ∼700nm long and 150-300nm in diameter, with a wall thickness of ∼50nm and pore diameter of about 150-250nm. These constructs showed high stability against aggregation indicated by a zeta potential of -44mV and an excellent temperature stability upto 200°C. Furthermore, they were found to be enzymatically degradable, thereby precluding any long term toxicity effects. These unique fibrin nanostructures were analyzed for their ability to deliver tacrolimus, an immunosuppressive drug that is used widely to prevent the initial phase of tissue rejection during allogenic transplantation surgeries. Upon conjugation with tacrolimus, a drug encapsulation efficiency of 66% was achieved, with the invitro release studies in PBS depicting a sustained and complete drug release over a period of one week at the physiological pH of 7.4. At a more acidic pH, the drug release was very slow, suggesting their potential for oralintestinal drug administration as well. The in vivo drug absorption rates analyzed in Sprague Dawley rats further confirmed the sustained release pattern of tacrolimus for both oral and parenteral delivery routes. The novel fibrin nanoconstructs developed using a green chemistry approach thus proved to be excellent biodegradable nanocarriers for oral as well as parenteral administratio