Preparation, characterization, and pharmacokinetics of liposomal docetaxel for oral administration

Abstract

A docetaxel (DTX) liposomal formulation composed of egg phosphatidylcholine, sodium deoxycholate, and stearylamine was developed. Eudragit (0.5%) was coated to deliver the drug to the region between the distal small intestine and the colon. Lyophilized trehalose and mannitol were used as cryoprotectants because they preserve the particle integrity and good appearance. In vitro release studies showed that the amount of drug released from the coated liposomes was low in solution 1, which simulated the pH condition of the stomach. Especially during the average gastric emptying time, the amount of drug released decreased when Eudragit was added. The plasma DTX concentration was evaluated in pharmacokinetic studies. The plasma drug concentration after intravenous (i.v.) administration decreased rapidly within 120 min. Free DTX formulated using Tween 80 and the lyophilized Eudragit-coated liposomal formulation were compared after oral administration. The oral liposomal formulation had a longer half-life (t(1/2)) and three-fold higher oral bioavailability. Thus, lyophilized Eudragit-coated liposomal DTX could be a promising therapy for various solid tumors to improve patient convenience and quality of life.