INHIBITION OF TUMOR-CELL GROWTH INVITRO AND INVIVO BY 1-BETA-D-ARABINOFURANOSYLCYTOSINE ENTRAPPED WITHIN PHOSPHOLIPID VESICLES

Abstract

Phospholipid vesicles were used as a carrier vehicle to enhance the cytotoxic activity of 1-.beta.-D-arabinofuranosylcytosine (ara-C) and 1-.beta.-D-arabinofuranosylcytosine 5''-triphosphate [ana-CTP] against several tumor cell lines. The activity of both compounds in free solution or entrapped within phospholipid vesicles was compared against L1210 [mouse leukemia] cells, Ehrlich ascites cells and SV40-transformed 3T3 [fibroblast] cells in vitro. The activity of vesicle-entrapped ara-C against L1210 cells was also studied in vivo. The results obtained in vitro with ara-C indicated no difference in the concentration needed to inhibit growth of cells by 50% [ID50] between free ara-C and vesicle-entrapped ara-C. ara-CTP entrapped in phospholipid vesicles was a more potent inhibitor of L1210 in culture (ID50, 2 x 10-8 M) compared to the relatively inactive free ara-CTP (ID50, > 10-7 M). Experiments with L1210 cells in mice showed that, after a single i.p. dose (10 mg/kg) of vesicle entrapped ara-C, the average survival time of mice inoculated with 105 L1210 cells was increased by over 90%. In control experiments, free ara-C or vesicles plus free ara-C (10 mg/kg) did not prolong survival of mice.