Abstract:

Objective   To prepare paclitaxel-loaded mixed micelles using D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and phosphatidylcholine (PC) and study the effect on oral absorption in rats. Methods   Paclitaxel-loaded mixed micelles were prepared by the film dispersion method. Zeta potential and the diameter distribution of TPGS/PC mixed micelles were measured using the laser size scattering determinator. Morphology of micelles was observed by the transmission electron microscope. Dialysis method was used to evaluate the release behavior of drug-loaded micelles in vitro. The absorption kinetics was obtained by the in situ perfusion method in rats. Plasma paclitaxel concentration was determined by HPLC and the pharmacokinetics in rats was studied. Results   Mixed micelles were almost spherical with an average diameter of 78.34 nm and the Zeta potential was -7.84 mV. Compared to the bulk drug, paclitaxel mixed micelles accelerated Ka, prolonged tmax and increased Cmax  and AUC0-∞（P＜0.05）.  Conclusion   TPGS/PC mixed micelles can improve the oral absorption of paclitaxel, and increase its oral bioavailability.

Key words: Paclitaxel；D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)； Mixed micelles； Oral absorption