STUDIES ON POLYPHASE LIPOSOME OF CAMPTOTHECIN, PL-CSA

Although camptothecin, an alkaloid extracted from the stem of Camptotheca acuminata Decne, was successfully used clinically as a chemotherapeutic agent for human cancer, terrible harmful side effects were observed in the treatment. Camptothecin sodium(CS), in the form of polyphase liposome was studied in this paper. It is assumed that CS in liposome-entrapped form might have more powerful antitumor activity and less toxicity than free CS.CS polyphase liposome(PL-CSA) was composed of camptothecin sodium, lecithin cholesterol, Tween-80, Span-80, PVP, etc. PL-CSA was found to be active in prolonging survival time in mice bearing experimental tumor ECA, being 50～78% longer than controls when injected peritoneally(0.75～1.0 mg/kg/d). However, CS(in free form) showed no effect against ECA. Both PL-CSA and CS were shown to be active against ECS. In addition, the toxicity of PL-CSA in mice was found to be weaker than CS. Other safety tests of PL-CSA were also carried out in rabbits and mice, no side-effect was observed.In the preparation of PL-CSA, 32～47% of the total amout of CS were entrapped in liposomes, 20～27% were adsorbed on liposomes, 17～24% were entrapped(or adsorbed) in micelles and 14～17% were shown to be in free form. The number and volume-average diameters of liposomes were 1.3 μm and 1. 7 μm, respectively.After a single intravenous administration of PL-CSA(25 mg/kg) to mice bearing ECA, the concentration of camptothecin was found to be highest in bile and intestinal contents, moderate in gastrointestinal tract, lung, spleen, liver, kidney, heart, and lowest in bone marrow, tumor and blood.