Efficacy of rifabutin-loaded microspheres for treatment of Mycobacterium avium-infected macrophages and mice.
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.
Barrow
Esther L W
EL
Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
Barrow
William W
WW
Quenelle
Debra C
DC
Westbrook
Louise
L
Winchester
Gary A
GA
Staas
Jay K
JK
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D015169:Colony Count, Microbial; D005260:Female; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D009000:Monocytes / Q000382:microbiology; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D009168:Mycobacterium phlei / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D017828:Rifabutin / Q000008:administration & dosage* / Q000494:pharmacology*; D015610:Serum Bactericidal Test
D000904:Antibiotics, Antitubercular; D017828:Rifabutin