TPGS-chitosan cross-linked targeted nanoparticles for effective brain cancer therapy

- Fabricated synergistic bioadhesive nanoparticles for brain targeted drug delivery
- TPGS-chitosan were synthesized and confirmed by FTIR, NMR and MALDI-TOF.
- Cellular uptake and cytotoxicity of the nanoparticles were performed.
- Pharmacokinetics was performed to study the bioavailability of the formulations.
- Synergistic effect of nanoparticles has enhanced the delivery of docetaxel into brain cancer cells.

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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