Preparation and evaluation of carboxymethyl chitosan-rhein polymeric micelles with synergistic antitumor effect for oral delivery of paclitaxel.

An amphiphilic carboxymethyl chitosan-rhein (CR) conjugate was prepared, characterized, and evaluated as a potential carrier material for oral delivery of paclitaxel (PTX). CR conjugate self-assembled in aqueous environment into CR polymeric micelles (CR PMs). The drug loading capacity and entrapment efficiency of PTX-loaded CR PMs were 35.24 ± 1.58% and 86.99 ± 12.26%, respectively. Pharmacokinetic results indicate that PTX-loaded CR PMs could significantly enhance the oral bioavailability of PTX. Confocal imaging of intestinal sections verified many of CR PMs were absorbed as whole through the intestinal membrane. The cytotoxicity assays in Caco-2 cells and in vivo antitumor efficacy showed that PTX-loaded CR PMs had a stronger antitumor efficacy. A synergistic antitumor effect between CR conjugate and PTX was proven in MCF-7 cells and antitumor efficacy studies. The investigation of CR conjugate developed in this study showed that CR PMs are promising for oral delivery of water-insoluble antitumor drugs.