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.
Phillips
N C
NC
Montreal General Hospital Research Institute, McGill University, Quebec, Canada.
Skamene
E
E
Tsoukas
C
C
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002214:Capsules; D004337:Drug Carriers; D004357:Drug Synergism; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen; D014018:Tissue Distribution; D015215:Zidovudine / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity
D002214:Capsules; D004337:Drug Carriers; D008081:Liposomes; D015215:Zidovudine