Enhancement of anti-tumor activity of 1-β-d-arabinofuranosylcytosine by encapsulation in liposomes

Abstract

1‐β‐D‐Arabinofuranosylcytosine (ara‐C) was encapsulated in four different types of unsonicated artificial vesicles of phospholipid (liposomes) to compare the anti‐tumor effect on mouse leukemia L1210 inoculated in CD2F, mice with that of free ara‐C. The anti‐tumor activity of ara‐C was markedly enhanced by encapsulation in liposomes when given in a single IP injection. Among the four types of liposomes, a physically stable and positively charged liposome consisting of sphingomyelin, stearylamine and cholesterol (20:2:15 molar ratio) most effectively enhanced the effect of ara‐C. A single IP dose of 50 mg/kg of ara‐C, encapsulated in this kind of liposome exhibited high activity, producing a survival rate of 60% of the treated mice at 60 days. This enhanced effect of ara‐C encapsulated in liposomes was also demonstrated when the drug was administered either IV or SC, and the range between the minimum effective and the maximum tolerable doses was wide enough to allow the safe use of the encapsulated ara‐C. Intra‐peritoneal administration of encapsulated ara‐C induced a more prolonged survival of mice inoculated with L1210 than did free ara‐C, regardless of whether it was given in single or multiple doses.