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
 

 

Deepthy Menon is a Professor at the Amrita Centre for Nanosciences & Molecular Medicine, Amrita Vishwa Vidyapeetham. She completed her Master’s degree in Physics from Cochin University of Science & Technology and Doctoral degree in Physics (Materials Science) from Indian Institute of Science, Bangalore. With post doctoral trainings from the Technical University of Eindhowen, The Netherlands; National Cancer Institute, Maryland, USA, and International School of Photonics, Cochin University, she joined Amrita in 2006 to work at the interface of materials science and biology. Her research work applies the use of advanced materials and technologies to various realms of biomedical problems such as cancer, regenerative medicine, etc. Dr. Menon’s research laboratory focuses on the design and development of multifunctional nanomaterials for cancer diagnosis and therapy based on quantum dots, magnetic and plasmonic nanomaterials. The use of biodegradable polymeric nanomaterials for drug delivery applications is also heavily explored. Her research also addresses the fabrication and evaluation of nanophase metallic materials for developing more effective biomedical implants in orthopedics, dental and vascular applications. A recent innovation by her group is the development of high strength biodegradable polymeric yarns/nanothreads by the process of electrospinning which finds use in drug eluting sutures, vascular grafts, implantable drug loaded patches, etc.

Dr. Deepthy has received several recognitions in her research career which includes the Young Research Award from International Union of Materials Research Society (1999), Young Scientist Fellowship from Department of Science & Technology [DST] (2002), Rapid Young Investigator grant from Department of Biotechnology [DBT] (2007) and BOYSCAST fellowship from Department of Science & Technology (2010). Her lab group has produced over 70 research publications, 45 conference presentations, 4 book chapters and 5 provisional or full patents. She is a member of the Materials Research Society, Society for Biomaterials, Photonics Society of India and American Chemical Society.

Extra Mural Research Funding: "Transformative Approaches for Design and Development of 2-D Carbon Photovoltaics" Awarded by Science and Engineering Research Board (SERB)-2018, Status: Principal Investigator.

Early Career Award: "Chemical Vapor Deposition Assembled 2D Layered Semiconductors Enabled Electrochemical Solar Cells" Science and Engineering Research Board (SERB)-2018.Status: Principal Investigator.

Publications

Publication Type: Journal Article

Year of Publication Title

2019

N. Parayath, Padmakumar, S., Nair, S. V., Dr. Deepthy Menon, and Amiji, M. M., “Strategies for Targeting Cancer Immunotherapy Through Modulation of the Tumor Microenvironment”, Regenerative Engineering and Translational Medicine, pp. 1-21, 2019.[Abstract]


Cancer immunotherapeutic strategies have shifted the focus of cancer treatment from eradicating the tumor cell by conventional cytotoxic chemotherapy, to educating the immune system to eliminate tumor, thereby preventing the recurrence of cancer. The understanding of tumor microenvironment and its components which generate an immunosuppressive environment is critical in further developing efficient immunotherapies. In this review, we have classified the current immunotherapies based on their effect in modulating the tumor microenvironment. Additionally, we propose the inclusion of nanotechnology and tissue engineering approaches, which provide unique strategies to enhance the therapeutic efficacy and could lead to developing nano/engineered immunotherapies for improved clinical outcomes. Specifically, we focus on criteria for designing nano/engineered immunotherapies and discuss targeted delivery strategies that can optimize the bioavailability of immunotherapies and, in turn, improve the therapeutic outcomes in the treatment of cancer.

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2019

S. Padmakumar and Dr. Deepthy Menon, “Nanofibrous Polydioxanone Depots for Prolonged Intraperitoneal Paclitaxel Delivery.”, Curr Drug Deliv, 2019.[Abstract]


<p><b>BACKGROUND: </b>Prolonged chemodrug delivery to the tumor site is a prerequisite to maintain its localised therapeutic concentrations for the effective treatment of malignant solid tumors.</p>

<p><b>OBJECTIVE: </b>The current study aims to develop implantable polymeric depots through conventional electrospinningmfor sustained drug delivery, specifically to peritoneum.</p>

<p><b>METHODS: </b>Non-woven electrospun mats were fabricated by simple electrospinning of Polydioxanone solution loaded with the chemodrug, Paclitaxel. The implants were subjected to analysis of morphology, mechanical properties, degradation and drug release in phosphate buffer and patient derived peritoneal drain fluid samples. In vivo studies were conducted by surgical knotting of these implants to peritoneal wall of healthy mice.</p>

<p><b>RESULTS: </b>Non-woven electrospun mats with a thickness of 0.65±0.07mm, weighing ~ 20 mg were fabricated by electrospinning 15w/v% polymer loaded with 10w/w% drug. These implants possessing good mechanical integrity showed a drug entrapment efficiency of 87.82±2.54 %. In vitro drug release studies in phosphate buffer showed a sustained profile for ~4 weeks with a burst of 10% of total drug content whereas, this amounted to ˃60% in patient samples. Mice implanted with these depots remained healthy during the study period. The biphasic drug release profile obtained in vivo showed a slow trend, with peritoneal lavage and tissues retaining good drug concentrations for a sustained period.</p>

<p><b>CONCLUSION: </b>The results indicate that non-woven electrospun mats developed from biodegradable Polydioxanone polymer can serve as ideal candidates for easily implantable drug depots to address the challenges of peritoneal metastasis in ovarian cancer.</p>

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2019

D. Narayanan, Pillai, G. J., Shantikumar V Nair, and Dr. Deepthy Menon, “Effect of Formulation Parameters on Pharmacokinetics, Pharmacodynamics, and Safety of Diclofenac Nanomedicine”, Drug Deliv Transl Res, 2019.[Abstract]


This study reports the development of a nanoformulation of diclofenac sodium, a potent non-steroidal anti-inflammatory drug, at its clinical dose, utilizing a FDA approved polymer, hydroxyethyl starch. The study specifically focused on the control of pharmacokinetics, pharmacodynamics, and biodistribution by particle surface functionalization and alteration of excipient levels in the final formulation. Stable diclofenac sodium-loaded hydroxyethyl starch nanoparticles (nanodiclo) of size 170 ± 5&nbsp;nm and entrapment efficiency 72 ± 3% were prepared. Free diclofenac, nanodiclo, nanodiclo surface functionalized by PEGylation, nanodiclo with excipients removed, and finally PEGylated nanodiclo with excipients removed were all tested comparatively at two different doses. The results showed substantial impact of both excipients and PEGylation on the pharmacokinetics and pharmacodynamics in vivo. Further, the results proved that excipient removed PEGylated nanodiclo at lower dose achieved clinical therapeutic levels in blood for up to 120&nbsp;h, with minimal accumulation in critical organs, and much better efficacy than other controls.

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2019

S. Padmakumar, Parayath, N. N., Shantikumar V Nair, Dr. Deepthy Menon, and Amiji, M. M., “Enhanced Anti-tumor Efficacy and Safety with Metronomic Intraperitoneal Chemotherapy for Metastatic Ovarian Cancer using Biodegradable Nanotextile Implants.”, Journal of Controlled Release, vol. 305, pp. 29-40, 2019.[Abstract]


The objective of this study was to evaluate intraperitoneal (IP) metronomic chemotherapy using sustained release paclitaxel (PTX) delivery from electrospun biodegradable polymeric yarns woven into suturable nanotextiles. Following confirmation of in vitro PTX efficacy in ID8-VEGF epithelial ovarian cancer cells, in vivo studies were performed upon surgical peritoneal implantation of nanotextile implants in orthotopic, syngeneic ID8-VEGF tumor-bearing C57BL/6 mice. In comparison to the clinical PTX-solution, there was a significant enhancement of anti-tumor efficacy and safety with PTX-nanotextiles. After 35-days, the peritoneum of tumor-bearing mice with PTX-nanotextiles was completely devoid of tumor nodules and ascitic fluid. Additionally, VEGF levels measured in peritoneal lavage fluid were 300-fold lower compared to PTX-solution and 600-fold lower as compared to untreated tumor-bearing animals. PTX-solution treated group also developed severe metastatic lesions and progressive ascitic fluid buildup. More importantly, no signs of systemic/ organ toxicity were observed in PTX-nanotextile implanted mice, unlike the systemic toxic effects induced by PTX-solution. Collectively, our results show the therapeutic and safety advantages offered by combining clinically translatable metronomic low-dose chemotherapy and IP pharmacokinetics using biodegradable nanotextile implants in addressing the challenges of late-stage ovarian cancer.

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2019

S. Padmakumar, Dr. Bindhu Paul, Pavithran, K., Vijaykumar, D. Kottarathi, Rajanbabu, A., Sivanarayanan, T. Balakrishn, Kadakia, E., Amiji, M. M., Shantikumar V Nair, and Dr. Deepthy Menon, “Long-term Drug Delivery using Implantable Electrospun Woven Polymeric Nanotextiles”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 15, no. 1, pp. 274-284, 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 60 days 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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2018

Manju V., Anitha A., Dr. Deepthy Menon, Dr. Subramania Iyer K., Shantikumar V Nair, and Dr. Manitha B. Nair, “Nanofibrous yarn reinforced HA-gelatin composite scaffolds promote bone formation in critical sized alveolar defects in rabbit model”, Biomedical Materials, vol. 13, no. 6, p. 065011, 2018.[Abstract]


Alveolar ridge resorption and crestal bone loss necessitate the use of bone graft substitutes for dental rehabilitation. The aim of this study was to compare the bone regenerative property of nanofibre incorporated two 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 fibres as well as commercial nanoHA-collagen graft. Interestingly, the mineralisation and the mineral density were significantly higher 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

J. Joseph, Krishnan, A. G., Cherian, A. M., Rajagopalan, B., Jose, R., Varma, P., Maniyal, V., Balakrishnan, S., Shantikumar V Nair, and Dr. Deepthy Menon, “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

A. Jose, Surendran, M., Fazal, S., Prasanth, B. - P., and Dr. Deepthy Menon, “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

S. Padmakumar, Parayath, N., Leslie, F., Shantikumar V Nair, Dr. Deepthy Menon, and Amiji, M. M., “Intraperitoneal Chemotherapy for Ovarian Cancer using Sustained-Release Implantable Devices”, Expert Opinion on Drug Delivery, vol. 15, no. 5, pp. 481-494, 2018.[Abstract]


INTRODUCTION: 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.

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2017

S. Fazal, Dr. Bindhu Paul, Shantikumar V Nair, and Dr. Deepthy Menon, “Theranostic Iron Oxide/Gold Ion Nanoprobes for MR Imaging and Noninvasive RF Hyperthermia.”, ACS Applied Materials and 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

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

C. C. Mohan, Cherian, A. Mary, Kurup, S., Joseph, J., Nair, M. B., Vijayakumar, M., Shantikumar V Nair, and Dr. Deepthy Menon, “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

G. J. Pillai, Dr. Bindhu Paul, Shantikumar V Nair, and Dr. Deepthy Menon, “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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2016

S. Padmakumar, Joseph, J., Neppalli, M. H., Mathew, S. E., Shantikumar V Nair, Dr. Sahadev Shankarappa, and Dr. Deepthy Menon, “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.

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2015

M. C.C, A.M., C., A, P., ,, Shantikumar V Nair, K, C., and Dr. Deepthy Menon, “Nanotextured Stainless Steel for Improved Corrosion Resistance and Biological Response in Coronary Stenting”, Nanoscale, vol. 7, no. 2, pp. 832-841, 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

Binulal Nelson Sathy, 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

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

D. Narayanan, Shantikumar V Nair, and Dr. Deepthy Menon, “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

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

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

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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2013

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

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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Publication Type: Patent

Year of Publication Title

2018

Dr. Deepthy Menon, Joseph, J., and Shantikumar V Nair, “Electrospinning Apparatus and Method for Producing Multi-Dimensional Structures and Core-Sheath Yarns”, 2018.

2016

Dr. Manitha B. Nair, Dr. Deepthy Menon, and Shantikumar V. Nair, “Porous Composite Fibrous Scaffold for Bone Tissue Regeneration”, U.S. Patent 15/341,866 2016.

2015

Dr. Manitha B. Nair, Dr. Deepthy Menon, and Shantikumar V. Nair, “Porous Composite Fibrous Scaffold for Bone Tissue Regeneration”, U.S. Patent 5919/CHE/20152015.

2015

Dr. Deepthy Menon, Joseph, J., and Nair, S., “Electrospinning Apparatus and Method for producing Multidimensional structures”, U.S. Patent 14/751,0692015.

2014

Dr. Deepthy Menon, Shantikumar V. Nair, Dr. Manzoor K., Rani, V. V. Divya, and Lakshmanan, V. Kumar, “Nano surface modified metallic titanium implants for orthopaedic or dental applications and method of manufacturing thereof”, U.S. Patent PCT/IN2012/0007862014.[Abstract]


The present invention relates to a metallic implant product developed with surface nano features by means of wet hydrothermal technique, which provides better bio-compatibility and improved osteo-integration for specific use in orthopaedic and dental applications. Methods of creating nano features on surfaces of titanium di-oxide (Titania) on Ti implants and the corresponding improved implant behaviour as a consequence under in vivo conditions are demonstrated and proven in this invention.

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2014

Dr. Deepthy Menon, Joseph, J., and Nair, S., “Electrospinning Apparatus and Method for producing Multidimensional structures”, U.S. Patent 3131/CHE/20142014.

2014

Dr. Manzoor K., Ashokan, A., Dr. Deepthy Menon, and Shantikumar V Nair, “The art, method, manner, process and system of multifunctional nanobiomaterial for molecular imaging and drug- delivery”, U.S. Patent PCT/IN2013/0001422014.[Abstract]


The present invention relates to a nano-sized material that can provide contrast enhancement for multiple molecular imaging mthods and also deliver therapeutic nucleic acids or chemodrugs at a specific site of disease such as cancer. In particular, the present invention relates to a nanosized synthetic calcium apatite based materials showing contrast imaging for visible to near-infrared fluroscence, magnetic resonance imaging and x-ray imaging together with targeted delivery of nucleic acid drugs (DNA or RNA) to specific cancer types.

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2012

Dr. Manzoor K., Shantikumar V Nair, Dr. Deepthy Menon, and Asok, A., “THE ART, METHOD, MANNER, PROCESS AND SYSTEM OF MULTIFUNCTIONAL NANOMEDICINE FOR MOLECULAR IMAGING AND SCINTILLATION THERAPY”, U.S. Patent 26/CHE/20122012.

2011

Dr. Deepthy Menon, Chennazhi, K., Mohan, C. C., R, S. P., and Shantikumar V Nair, “THE ART, METHOD AND MANNER OF TITANIUM-BASED CARDIOVASCULAR STENTS WITH NANOSTRUCTURED SURFACES”, U.S. Patent 2355/CHE/20112011.

2011

Dr. Deepthy Menon, Shantikumar V. Nair, K, M., V., D. V., and Lakshmanan, V. - K., “THE ART, METHOD AND MANNER OF NANOSURFACE MODIFICATION OF TITANIUM IMPLANTS FOR ORTHOPEDIC OR DENTAL APPLICATIONS”, U.S. Patent 1644/CHE/20112011.

2010

Shantikumar V. Nair, Chennazhi, K., Dr. Deepthy Menon, and G, P., “ART, METHOD, MANNER, PROCESS AND SYSTEM OF PREPARATION OF FIBRIN NANOCONSTRUCTS FOR TISSUE ENGINEERING AND DRUG DELIVERY APPLICATIONS”, U.S. Patent 3451/CHE/20102010.

2010

Shantikumar V. Nair, Chennazhi, K., Dr. Deepthy Menon, and R, S. P., “THE ART, MANNER, METHOD, PROCESS AND SYSTEM FOR THE FABRICATION OF ELECTROSPUN NANOFIBROUS FIBRIN SCAFFOLD FOR TISSUE ENGINEERING APPLICATIONS”, U.S. Patent 3413/CHE/20102010.

2009

M. Koyakutty, Anusha Ashokan, Dr. Deepthy Menon, and Nair, S., “THE ART, METHOD, MANNER, PROCESS AND SYSTEM OF MULTIFUNCTIONAL NANOBIOMATERIAL FOR MOLECULAR IMAGING AND DRUG-DELIVERY (Filed)”, U.S. Patent 2633/CHE/20092009.

Dr. Deepthy Menon
Professor, Nanosciences, Center for Nanosciences, Kochi

deepthymenon@aims.amrita.edu