Preparation of Topotecan Loaded Long-Circulating Liposomes and Its Pharmacokinetic Evaluation in Rats

Topotecan, a topoisomerase І inhibitor, is presently undergoing clinical evaluation worldwide. Unfortunately, TPT is extremely unstable in physiological conditions. Conversion of the lactone form into the carboxylate form occurs rapidly at physiological pH. In this study we describe preparation of classical and long-circulating liposomes with more stability of lactone form of drug in plasma in comparison with free drug. Both, classical and long-circulating liposomes showed higher in vitro cytotoxicity. Because of increased blood circulation time, the area under the plasma concentration curve of classical liposomes and long-circulating liposomes were 8 and 16 times, respectively, of those of free drug.

Keywords:

Long-circulating Liposome , Topotecan , Pharmacokinetic