Therapeutic efficacy of liposome-encapsulated kanamycin against Mycobacterium intracellulare infection induced in mice.
Liposome-encapsulated kanamycin (KM) was examined for therapeutic efficacy against experimental infection induced with Mycobacterium intracellulare in mice. Liposomal KM injections (once weekly for up to 8 wk) led to a greater reduction in the degree of gross pulmonary lesions and in the growth of the organisms in the visceral organs (lungs, liver, spleen, and kidneys) of infected mice than did either free KM alone or free KM mixed with empty liposomal vesicles. The therapeutic effect of the liposome-encapsulated KM was dose dependent for doses from 50 to 200 micrograms KM/mouse/injection. Liposome encapsulation markedly changed the tissue distribution of KM, in particular in the reticuloendothelial organs, such as liver and spleen. In these organs, accumulation and retention of liposome-entrapped KM was remarkably higher than that of free KM. Moreover, considerably prolonged retention was seen for liposome-encapsulated KM in serum and lungs. Encapsulation of KM into liposomal vesicles increased incorporation of the drug into the host peritoneal macrophages and enhanced the antimicrobial activity of the agent against M. intracellulare phagocytosed into macrophages.
Tomioka
H
H
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
Saito
H
H
Sato
K
K
Yoneyama
T
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D007612:Kanamycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008081:Liposomes; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015269:Mycobacterium avium Complex / Q000187:drug effects; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010587:Phagocytosis; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D007612:Kanamycin