A multistage oral delivery system of PTX for improving oral bioavailability and enhancing anticancer efficacy

Abstract

Objective Bromotetrandrine (W198) was reported as a P-glycoprotein (P-gp) inhibitor. We aimed to prepare oral W198 micelles following by paclitaxel (PTX) micelles (W198/PTX micelles) to improve the clinical application of PTX. Significance The poor water solubility, intestinal permeability, and multidrug resistance (MDR) of PTX can be improved in the multistage oral delivery system. Methods The novel W198/PTX oral micelles were developed by water-bath ultrasound method and were evaluated in vivo and in vitro in 4T1 orthotopic tumor-bearing mice model. Results PTX micelles and W198 micelles were prepared to be round and uniform. W198 micelles pre-administrated group showed higher cellular uptake efficiency of PTX on Caco-2 cells and more prominent cytotoxicity compared with W198-untreated group on 4T1 cells. The oral bioavailability of W198/PTX micelles group was nearly 5.7-folds higher than the PTX micelles only group. In addition, W198/PTX micelles showed enhanced anticancer efficacy. Conclusions We established a multistage oral delivery system to improve oral bioavailability and anticancer efficacy of PTX.