Multi-functional chitosan polymeric micelles as oral paclitaxel delivery systems for enhanced bioavailability and anti-tumor efficacy.

Chitosan is widely used as a permeation enhancer for oral drug delivery, although its drawbacks include a limited enhancement of drug bioavailability and an inability to form micelles. In this study, we designed a novel chitosan derivative (GA-CS-TPGS copolymer) and constructed paclitaxel micelles (PTX-Micelles) designed to have multiple functions associated with the GA-CS-TPGS copolymer (enhanced bioadhesion, inhibited P-gp efflux and drug metabolism in liver) and the micelles (enhanced solubility and permeability) to enhance the bioavailability and anti-tumor efficacy of PTX. The results showed that the PTX-Micelles system could alter the in vivo pharmacokinetic performance and therapeutic effect of PTX via its predesigned functions. The bioavailability of PTX was enhanced approximately 3.80-fold by the PTX-Micelles, and an enhanced anti-lung tumor efficacy of PTX-Micelles was observed when compared to Taxol®. The results of this study indicate that constructing micelles with a multifunctional chitosan derivative may be a promising approach to enhance the oral bioavailability and anti-tumor efficacy of poorly soluble drugs.