Preparation and studies of docetaxel proliposome

Abstract

The taxanes, paclitaxel and docetaxel, are anticancer agents used in clinical trials against ovarian carcinoma, breast, lung and head/neck cancer. Docetaxel, more soluble than paclitaxel in water, is formulated using Tween 80 and ethanol. Tween 80, albeit less toxic than Cremophor EL, may be responsible of some toxic effects. To eliminate these vehicles and improve the drug's antitumor efficacy, taxanes have been incorporated in liposomes, however the stability of the common liposomes was poor. We have prepared a well-characterized novel lyophilized liposome-based docetaxel formulation that is sterile and easy-to-use. Of the several formulations examined, docetaxel-liposomes composed of ePC/CHOL 15:3 and co-surfactant poloxamer188/ePC/3:5 were chosen for further studies. This composition was found to give more stable liposomes than other formulations. It gave 95% entrapment efficiency and particle size of 200 nm after lyophilization. The pharmacokinetic parameters intravenously administration to the rats were determined and compared with those of commercial docetaxel formulations. Encapsulation of docetaxel in proliposomes produced marked differences over the commercial preparations with an increased Cmax, prolonged elimination half-life, and an increased value for Area Under Curve (AUC). The obtained values for mean residence time (MRT) indicated that docetaxel remains longer for liposomal formulation. The docetaxel proliposome (PRDL) was more effective than docetaxel injection (DXL-INJ) and plain docetaxel liposome (PDL) in the high, medium and low docetaxel dose trials.