title: Treatment of Mycobacterium avium-intracellulare complex infection in beige mice with free and liposome-encapsulated streptomycin: role of liposome type and duration of treatment.
abstract: Current treatments for Mycobacterium avium-intracellulare complex (MAC) infections are generally ineffective. Thus, the potential of free or liposome-encapsulated streptomycin to treat acute MAC infection was investigated in beige mice. Free streptomycin administered intramuscularly 5 days a week (150 mg/kg) was effective in the liver, spleen, and lungs. At 4 weeks, liposome-encapsulated streptomycin, administered intravenously in weekly doses (15 mg/kg), reduced the colony-forming units in the liver and spleen by about the same extent as a 50- to 100-fold higher dose of free drug. With 4 weekly injections of liposomes, the colony-forming units in the liver and spleen were lower by 2.4 and 2.9 log units, respectively, compared to untreated controls, even by the end of 12 weeks. The effects of unilamellar and multilamellar liposomes were similar. These observations suggest that liposome encapsulation not only targets streptomycin to infected cells but also increases the residual activity of the drug.
authors.affiliation: Cancer Research Institute, University of California, San Francisco.
authors.forename: N
authors.initials: N
authors.lastname: Düzgüneş
authors.forename: D R
authors.initials: DR
authors.lastname: Ashtekar
authors.forename: D L
authors.initials: DL
authors.lastname: Flasher
authors.forename: N
authors.initials: N
authors.lastname: Ghori
authors.forename: R J
authors.initials: RJ
authors.lastname: Debs
authors.forename: D S
authors.initials: DS
authors.lastname: Friend
authors.forename: P R
authors.initials: PR
authors.lastname: Gangadharam
mesh_terms: D000818:Animals; D004337:Drug Carriers; D005614:Freeze Fracturing; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008081:Liposomes; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000254:growth & development; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D013154:Spleen / Q000378:metabolism / Q000382:microbiology; D013307:Streptomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D013307:Streptomycin