Liposomal hamycin: reduced toxicity and improved antifungal efficacy in vitro and in vivo.
Hamycin has been used to treat a variety of yeast and other fungal infections by oral, topical, and intraperitoneal routes. However, its parenteral use has been reported to be associated with high toxicity. Multilamellar liposomes composed of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidyl glycerol, and various amounts of cholesterol were used as drug carriers for hamycin. The antifungal activity of hamycin was maintained after liposome encapsulation (MIC range, 0.6-1.2 micrograms/ml), and toxicity was reduced in vitro and in vivo as the concentration of cholesterol was increased to an appropriate ratio. Mice were treated with various doses of free or liposomal hamycin 2 days after infection. Although free drug did not significantly improve survival, liposomal hamycin at an equivalent dose (0.6 mg/kg) increased the survival from 18 to 38 days. Higher doses (1.2 and 1.8 mg/kg) showed further improvement in survival and reduction in numbers of colony-forming units in the kidneys. Liposome encapsulation resulted in improved therapeutic index of hamycin.
Mehta
R T
RT
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
McQueen
T J
TJ
Keyhani
A
A
Lopez-Berestein
G
G
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D002478:Cells, Cultured; D004337:Drug Carriers; D004912:Erythrocytes / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D008081:Liposomes; D051379:Mice; D011090:Polyenes / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D011090:Polyenes; C100114:hamycin