抗癌药物新剂型——多相脂质体的研究 (Ⅶ) 喜树碱多相脂质体的研究(简报)

<正> 前报研究了油酸多相脂质体、复方唐松草新碱多相脂质体和复方氟尿嘧啶多相脂质体,本研究是继续开拓多相脂质体在抗癌药方面的应用范围,选用的药物是喜树碱。美国癌症研究所Wall等发现喜树Camptotheca acuminata树干的醇浸出液对小鼠腺癌有抑制作用,并分离出有效成分生物碱——喜树碱Camptothecin。Gallo等报告,喜

AN INVESTIGATION OF POLYPHASE LIPOSOME—ANEWDOSAGE FORM ANTITUMOR AGENTS Ⅶ. STUDIES ON POLYPHASE LIPOSOME OF CAMPTOTHECIN

Camptothecin, an alkaloidal extract from the stem wood of the Chinese tree Camptotheca acuminata Decne, was used clinically as a chemotherape-utic agent in man with cancer. But terrible harmful reactions and side-effects were observed in the treatment. Camptothecin sodium (CS) in the presence of polyphase liposome was studied in this paper. it is assumed that CS in liposome-entrapped form might have more powerful antitumur activity, and slighter toxicity than free CS. CS by polyphase liposome(PL-CS and PL-CSA)are composed of camptothecin sodium, leucitin, cholesterol, Tween-80, Span-80, PVP, etc. PL-CS and PL-CSA were active in increasing survival time in mice bearing experimental tumor ECA. They produced 50-103% long-time survivors in mice, when injected into mice peritoneally(0.75-1.0 mg/kg/day). However, CS(in free form) has no effect against the tumor ECA. PL-CS, PL-CSA were also active against the tumor ECS in common with CS. The inhibition rate of tumor weight are 51-59% (PL-CS) and 57-66% (PL-CSA) respectively. In addition, the toxicity from PL-CSA in mice is weaker than PL-CS and CS. The LD_(50) of PL-CSA in mice (peritoneally) was 130 mg/kg, that of PL-CS was 64 mg/kg, and that of CS was 82 mg/kg. Other safety tests of PL-CSA were also carried out in rabbits and mice, no harmful reaction as side-effect were obsrved. In the preparation of PL-CSA, CS entrapped in liposomes amounted to 32-47%, that adsorbed on liposomes amounted to 20-27%, that entrapped (or adsorbed)in micelles amounted to 17-24%, and that in free form amoun- led to 14-17%, The number and volume-average diameters of liposomes were 1.3μm and 1.7μm respectively. Distribution studies of PL-CSA given to mice bearing ECA showed that after a single intravenous administration (25mg/kg), the concentration of camptothecin was found to be the highest in the bile and intestinal contents, moderate in gastrointestinal tract, lung, spleen, liver, kidney, heart, and lowest in bone marrow, tumor, blood.