Toxicity and therapeutic effects in mice of liposome-encapsulated nystatin for systemic fungal infections.
The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively). The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg). Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.
Department of Clinical Immunology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston.
R T
RT
Mehta
R L
RL
Hopfer
T
T
McQueen
R L
RL
Juliano
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G
Lopez-Berestein
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D002214:Capsules; D008081:Liposomes; D051379:Mice; D008815:Mice, Inbred Strains; D009761:Nystatin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
D002214:Capsules; D008081:Liposomes; D009761:Nystatin