Li JL, Felgner PL, Richman DD, Hostetler KY; International Conference on AIDS.
Int Conf AIDS. 1990 Jun 20-23; 6: 184 (abstract no. Th.A.256).
Vical Inc., San Diego, CA, USA
OBJECTIVE: The LP-BM5 murine leukemia virus produces a disease in C57BL/6 mice with many features of AIDS (MAIDS) and has been shown to be responsive to treatment with zidovudine (AZT). Treatment of mice with 100 mg/kg/day by intraperitoneal (i.p.) injection prolonged survival while 10 mg/kg/day was less effective. Macrophages are heavily infected with LP-BM5. METHOD: To direct larger amounts of drug to macrophages, we encapsulated [3H]AZT monophosphate in liposomes and determined tissue and plasma levels at various times over a 48hr period. After infection with LP-BM5, AZT (100, 31.6 or 10 mg/kg/day in divided bid doses), liposomal AZT-monophosphate (L-AZT-MP) (10, 3.9, 1 and 0.39 mg/kg/day, single dose every other day) or controls were injected i.p. RESULTS: Tissue and plasma levels of L-AZT-MP were manyfold higher than those observed after AZT administration in a equimolar dose. Tissues rich in monocyte/macrophages retained the most drug. Tissue levels of L-AZT-MP were substantial 24 to 48 hours after a single dose of 10 mg/kg while AZT produced significant tissue levels for only 4 to 6 hours. In the MAIDS animals after 33 weeks, the largest number of surviving mice was in the 10 mg/kg/day L-AZT-MP group (67%); in the 100 and 31.6 mg/kg/day AZT group survival was much lower (7% and 23%) while the empty liposome control group had 28% surviving. CONCLUSIONS: Our results suggest that treatment with L-AZT-MP every other day is considerably more effective than treatment twice daily with AZT even at doses 10 times higher. L-AZT-MP may be useful as a treatment for the macrophage reservoir of HIV.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- HIV Infections
- Immunologic Deficiency Syndromes
- Leukemia Virus, Murine
- Liposomes
- Mice
- Mice, Inbred C57BL
- Murine Acquired Immunodeficiency Syndrome
- Retroviridae
- Retroviridae Infections
- Zidovudine
Other ID:
UI: 102181809
From Meeting Abstracts