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TPGS-chitosan Cross-linked Targeted Nanoparticles For Effective Brain Cancer Therapy.

Poornima Agrawal, R. Singh, Sonali, L. Kumari, G. Sharma, B. Koch, Chellapa V. Rajesh, A. K. Mehata, S. Singh, B. L. Pandey, M. Muthu
Published 2017 · Materials Science, Medicine

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Brain cancer, up-regulated with transferrin receptor led to concept of transferrin receptor targeted anticancer therapeutics. Docetaxel loaded d-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-chitosan) nanoparticles were prepared with or without transferrin decoration. In vitro experiments using C6 glioma cells showed that docetaxel loaded chitosan nanoparticles, non-targeted and transferrin receptor targeted TPGS-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity. The IC50 values of non-targeted and transferrin receptor targeted nanoparticles from cytotoxic assay were found to be 27 and 148 folds, respectively higher than Docel™. In vivo pharmacokinetic study showed 3.23 and 4.10 folds enhancement in relative bioavailability of docetaxel for non-targeted and transferrin receptor targeted nanoparticles, respectively than Docel™. The results have demonstrated that transferrin receptor targeted nanoparticles could enhance the cellular internalization and cytotoxicity of docetaxel via transferrin receptor with improved pharmacokinetics for clinical applications.
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