Bioadhesive micelles of d-α-tocopherol polyethylene glycol succinate 1000: Synergism of chitosan and transferrin in targeted drug delivery

•Developed synergistic bioadhesive micelles for brain targeted drug therapy.•TPGS-chitosan/transferrin were synthesized and confirmed by various spectroscopic techniques.•Cellular uptake, time-dependent bioadhesive studies and cytotoxicity of micelles were performed.•Pharmacokinetics studies were performed for micelles in rats.•Synergistic effect of micelles has enhanced the delivery of DTX into brain cancer cells.

The aim of this work was to prepare targeted bioadhesive d-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC50 values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24 h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48 h of treatments, respectively.

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