Inhibition of tumor cell growth in vitro and in vivo by 1-beta-D-arabinofuranosylcytosine entrapped within phospholipid vesicles.
Phospholipid vesicles have been used as a carrier vehicle to enhance the cytotoxic activity of 1-beta-D-arabinofuranosyl-cytosine (ara-C) and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate against several tumor cell lines. The activity of both compounds in free solution or entrapped within phospholipid vesicles was compared against L1210 cells, Ehrlich ascites cells, and SV40-transformed 3T3 cells in vitro. In addition, 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% between free ara-C and vesicle-entrapped ara-C. In contrast, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate 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 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (id50 greater than 10(-7) M). Experiments carried out with L1210 cells in mice showed that, after a single i.p. dose (10 mg/kg) of vesicle-entrapped ara-C, the average survival times of mice inoculated with 10(5) L1210 cells were 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.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003561:Cytarabine / Q000008:administration & dosage* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008811:Mice, Inbred DBA; D014677:Pharmaceutical Vehicles; D010743:Phospholipids; D013539:Simian virus 40
D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D010743:Phospholipids; D003561:Cytarabine