Abstract
Two poly(DL-lactide-co-glycolide) microsphere formulations (A, 10% wt/wt, and B, 23% wt/wt, 1-10 microns) were evaluated for intracellular delivery of rifabutin using the J774 murine and Mono Mac 6 (MM6) human monocytic cell lines. Within 7 days, formulation A released 100% in both cell lines and B released 53 and 67% in the J774 and MM6, respectively. Intracellular release of rifabutin with both formulations caused significant reduction of intracellularly replicating Mycobacterium avium (MAC). In MAC-infected beige mice, formulation B (50 mg, intraperitoneal days 0 and 7) completely eliminated infection by 21 days (p < 0.001), similar to a rifabutin daily oral regimen.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibiotics, Antitubercular / administration & dosage*
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Antibiotics, Antitubercular / pharmacology*
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Cell Line
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Cell Survival / drug effects
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Chemistry, Pharmaceutical
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Colony Count, Microbial
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Female
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Macrophages / microbiology*
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Mice
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Mice, Inbred C57BL
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Microbial Sensitivity Tests
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Microspheres
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Monocytes / microbiology
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Mycobacterium avium-intracellulare Infection / drug therapy*
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Mycobacterium avium-intracellulare Infection / microbiology
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Mycobacterium phlei / drug effects
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Phagocytosis / drug effects
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Rifabutin / administration & dosage*
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Rifabutin / pharmacology*
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Serum Bactericidal Test
Substances
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Antibiotics, Antitubercular
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Rifabutin