EFFECT OF CHOLESTEROL CONTENT ON ANTI-TUMOR ACTIVITY AND TOXICITY OF LIPOSOME-ENCAPSULATED 1-BETA-D-ARABINOFURANOSYLCYTOSINE INVIVO

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 630-633
Abstract
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 h 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. Drug efflux and in vivo antitumor activity and toxicity of encapsulated ara-C is apparently influenced by the cholesterol content of the liposomal lipid bilayer.