POTENTIATION OF CYTOTOXICITY OF KAPOSIS-SARCOMA RELATED TO IMMUNODEFICIENCY SYNDROME (AIDS) BY LIPOSOME-ENCAPSULATED DOXORUBICIN

Kaposi's sarcoma is an independent criterion for the diagnosis of AIDS and develops in nearly 15 % of all cases. Current chemotherapy regime ns are associated with substantial taxicity, particularly bone marrow suppression, which limit their long-term use. In an attempt to reduce treatment-related toxicity and enhance uptake of the drug in tumor cel ls, free and liposome-encapsulated doxorubicin was tested in vitro. Th e liposomes were prepared with cardiolipin, phosphatidylcholine, and c holesterol. Kaposi's sarcoma (KS)-derived spindle cells were exposed t o free doxorubicin (DOX) and liposome-encapsulated doxorubicin (LED) f or various time intervals and analyzed for cellular cytotoxicity, thym idine incorporation, and cellular drug uptake. Cytotoxicity studies of KS cells with free DOX and LED showed an IC50 of 288 and 7.5 ng/ml, r espectively, hence demonstrating a 38-fold higher cytotoxicity by LED. Thymidine incorporation studies in KS cells demonstrated over one log higher toxicity to LED compared to free DOX. Cellular drug uptake stu dies showed that free DOX concentration peaked in 1 hr in KS cells whe reas LED continued to accumulate up to 4 hr. At 4 hr, anthracycline up take through LED was fivefold higher than the uptake of free drug. Sim ilarly LED uptake in the cells evaluated by direct fluorescent microsc opy was much more intense and more frequent than the uptake of free dr ug. Thus AIDS-KS cells appear to be exquisitely sensitive to LED, whic h may provide a higher therapeutic to toxicity index in clinical use.