1983 Volume 74 Issue 2 Pages 197-205
Liposome is a bilayered phospholipid vesicles, and was originally developed as a model for biomem-branes. Liposome has attracted attention in recent years as a potential carrier of anticancer drugs thereby enhancing the therapeutic effect. This study was designed to clarify the following problems associated with clinical application of liposome in future.
1) The influence of liposome-entrapped anticancer drugs on cytotoxic activity in in vitro system.
2) The effect of liposome-entrapped anticancer drugs in the host tissues.
3) The in vivo therapeutic efficacy of liposome-entrapped bleomycin in the treatment of testicular tumor transplanted in nude mice.
For cytotoxicity test, KU-2 cells, dervived from human renal cell carcinoma were used. Effect of free and liposome-entrapped bleomycin on the growth of KU-2 cells was determined. Enhanced effect was noted in the latter group. Also effect of free and liposome-entrapped bleomycin on the cell cycle traverse of KU-2 cells was determined by means of flow microfluorometry. Obvious effects of G2-block was noted in liposome-entrapped bleomycin.
Therapeutic effect of free and liposome-entrapped bleomycin on the testicular tumor bearing nude mice (KUNU-1) was examined. Antitumor effects of bleomycin was enhanced by entrapment of bleomycin into liposome, mean growth rates of the tumor by administration of free and liposome-entrapped bleomycin at day 5 were 91.1±8% and 76.1±14%, respectively.
Bleomycin, either free or liposome-entrapped, was injected into the peritoneal cavity of KUNU-1 mice in a dose of 5mg. When liposome-entrapped bleomycin was given, increase in the concentration of bleomycin was sixfold in the spleen; threefold in the liver; twofold in the kidney and one and half fold in the lung.
These results indicate that liposome entrapment modified the pharmacokinetics and enhanced the anticancer activity of the drug mediated by slow delivery rather than providing selective cytotoxic effect of the drug to tumors.
