Efficacy of rifabutin-loaded microspheres for treatment of Mycobacterium avium-infected macrophages and mice

Drug Deliv. 2007 Mar;14(3):119-27. doi: 10.1080/10717540600739815.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antitubercular / administration & dosage*
  • Antibiotics, Antitubercular / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Colony Count, Microbial
  • Female
  • Macrophages / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Microspheres
  • Monocytes / microbiology
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Mycobacterium avium-intracellulare Infection / microbiology
  • Mycobacterium phlei / drug effects
  • Phagocytosis / drug effects
  • Rifabutin / administration & dosage*
  • Rifabutin / pharmacology*
  • Serum Bactericidal Test

Substances

  • Antibiotics, Antitubercular
  • Rifabutin