Comparison of paclitaxel solid dispersion and polymeric micelles for improved oral bioavailability and in vitro anti-cancer effects

Abstract

The purpose of this study was to develop paclitaxel (PTX) formulations with solid dispersion (SD) and micelles (M) in order to improve solubility and oral absorption in rats. In addition, the enhanced anti-cancer effects of PTX formulations were compared in various breast cancer cell lines. The SD formulations with various copolymers were prepared using a solvent evaporation method, and micelles with Soluplus® mixed with d-α-tocopheryl polyethylene glycol-1000-succinate (TPGS) were prepared using a film hydration method. The physical properties of SD and M formulations were evaluated. The dissolution (%) of SD4 and SD9 formulations, and the solubility of M2 were significantly higher than those of PTX. The SD formulations and micelles were also stable for 3 and 1 month, respectively. The anti-cancer effects of SD4, SD9, and M2 significantly increased in breast cancer cells, whereas the blank formulations were not toxic to normal cells. The SD4, SD9 and M formulations improved the permeability of Cou-6 compared to Cou-6 solution in Madin-Darby canine kidney cells (MDCK line). The SD formulations and micelles had enhanced bioavailability (BA) compared to that of PTX, showing relative BA values of 667.3% (SD4), 359.6% (SD9), and 365.4% (M2). This study demonstrates the technologies to increase the anti-cancer effects and BA of PTX, via SD and micelle formulations, and, to our knowledge, is the first comparison of the two formulations.