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.
Mehta
R T
RT
Department of Clinical Immunology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston.
Hopfer
R L
RL
McQueen
T
T
Juliano
R L
RL
Lopez-Berestein
G
G
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