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

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.Graphical abstractIn this paper, we intended to synthesize a GA-CS-TPGS copolymer and construct paclitaxel micelles by using this copolymer. Aiming to use the enhanced bioadhesion and inhibited P-gp efflux and CYP3A enzyme activity caused by this copolymer to enhance the bioavailability and anti-tumor efficacy of paclitaxel.

Source: International Journal of Pharmaceutics - February 3, 2020 Category: Drugs & Pharmacology Source Type: research