Liposomal encapsulation of 3'-azido-3'-deoxythymidine (AZT) results in decreased bone marrow toxicity and enhanced activity against murine AIDS-induced immunosuppression.

The effect of liposome encapsulation on the bone marrow toxicity and antiviral activity of AZT in C57BL/6 mice was determined. Liposomal encapsulation of AZT enhanced localization in the liver, spleen, and lung, and reduced localization in bone marrow. AZT administered i.v. (0.08-50 mg/kg/day) had significant bone marrow toxicity (30-50% reduction in cellularity) after five injections, maximum toxicity occurring at greater than or equal to 2 mg/kg/day. Parallel reductions in the number of erythrocytes and leukocytes were observed. AZT encapsulated in liposomes had no bone marrow toxicity at doses of 0.08-10 mg/kg/day, and erythrocyte and leukocyte numbers remained normal. Infection of C57BL/6 mice with LP-BM5 murine leukemia virus suppressed T- and B-cell mitogenic responses. Treatment of LP-BM5 retrovirus-infected mice with 2 mg/kg AZT three times weekly partially protected the mitogenic response at 4 but not at 7 weeks postinfection. Treatment with liposomal AZT resulted in normal T- and B-cell mitogenic responses at both 4 and 7 weeks postinfection.