Effect of cholesterol content on antitumor activity and toxicity of liposome-encapsulated 1-beta-D-arabinofuranosylcytosine in vivo.
1-beta-D-Arabinofuranosylcytosine (ara-C) was encapsulated in anionic multilamellar liposomes prepared with different lecithin: cholesterol (L:C) ratios. The chemotherapeutic activity of encapsulated ara-C was compared with comparable doses of ara-C in 0.85% saline solution (single- and multiple-dose schedules) in mice bearing L1210 (i.p.) leukemia. Maximum survival was obtained in animals given injections of ara-C (40 mg/kg) encapsulated in liposomes with a L:C ratio of 1:1. The effect of L:C ratio on survival was not pronounced in multiple-dose schedules. Multiple doses (every 4.5 hr for 3 separate injections) of 40 mg/kg with L:C ratios of 1:1 and 1:0.5 were toxic, resulting in 83 and 50% mortality, respectively, of mice by Day 7. This study shows that drug efflux and in vivo antitumor activity and toxicity of encapsulated ara-C is influenced by the cholesterol content of the liposomal lipid bilayer.
D000818:Animals; D002784:Cholesterol / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007939:Leukemia L1210 / Q000188:drug therapy*; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D010713:Phosphatidylcholines / Q000008:administration & dosage
D008081:Liposomes; D010713:Phosphatidylcholines; D003561:Cytarabine; D002784:Cholesterol