Improved oral bioavailability and anticancer efficacy on breast cancer of paclitaxel via Novel Soluplus®-Solutol® HS15 binary mixed micelles system

The aim of this study was to develop a novel drug delivery system using two biocompatible copolymers of Solutol (R) HS15 and Soluplus (R) to improve solubility, oral bioavailability and anticancer activity of paclitaxel (PTX). The PTX-loaded mixed micelles (PTX-M) were prepared by ethanol thin-film hydration method. The optimal PTX-M were provided with small size (164.8 +/- 2.0 nm) and spherical shape at ratio of 1: 3 (Solutol (R) HS15: Soluplus (R)), thus increasing the solubility to 15.76 +/- 0.15 mg/mL in water. The entrapment efficiency and drug loading of PTX-M were 98.48 +/- 0.91% and 10.59 +/- 0.09% respectively. In vitro release study indicated a sustained release of PTX-M. Transcellular transport study showed that the efflux ratio were decreased by 89.72% dramatically in Caco-2 cell transport models, and the pharmacokinetics study of PTX-M compared with PTX, showed a 3.68-fold increase in relative oral bioavailability, indicating the mixed micelles may promote absorption in the gastrointestinal tract. In addition, the MIT assay demonstrated that the IC50 value of PTX-M was reduced by 40.21% (PTX-M: 22.6 +/- 2.1 mu g/mL, PTX: 37.8 +/- 1.4 mu g/mL), and in vivo anti-tumor study (15 days' therapy) showed PTX-M achieved higher anti-tumor efficacy (57.66%) compared with PTX (41.13%). Furthermore, a gastrointestinal safety assay also provided the reliability and safety of PTX-M. Collectively, these findings present an oral micelle formulation with increased solubility, oral bioavailability and anticancer activity of PTX. (C) 2016 Elsevier B.V. All rights reserved.