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Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Biochimica et Biophysica Acta - General Subjects, Elsevier

Source : Biochimica et Biophysica Acta - General Subjects, Elsevier, Volume 1840, Number 9, p.2730-2743 (2014)

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Keywords : 5-fluorouracil, acidity, animal experiment, animal model, Animals, antineoplastic activity, area under the curve, article, Biological Availability, blood compatibility, cancer cell, cancer combination chemotherapy, cell cycle, Cell Line, cell viability, chitosan, Colon cancer, Colonic Neoplasms, Combinatorial nanomedicine, concentration response, cross linking, curcumin, Delayed-Action Preparations, drug degradation, drug distribution, drug efficacy, drug formulation, drug mechanism, drug release, drug synthesis, fluorouracil, Hemolysis, Histology, Humans, in vitro study, maximum plasma concentration, Membrane Potential, Mice, Mitochondrial, mitochondrial membrane potential, mouse, nanoparticle, Nanoparticles, nonhuman, particle size, pH, Pharmacokinetics, priority journal, sustained drug release, Thiolated chitosan, time to maximum plasma concentration, Tumor, zeta potential

Campus : Mysuru

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Department of Sciences, Nanosciences and Molecular Medicine

Year : 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.



Cite this Research Publication : 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.

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