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Journal Article

Amphotericin B liposomes with prolonged circulation in blood: in vitro antifungal activity, toxicity, and efficacy in systemic candidiasis in leukopenic mice.

E W van Etten, M T ten Kate, L E Stearne, I A Bakker-Woudenberg
E W van Etten
Department of Clincal Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
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M T ten Kate
Department of Clincal Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
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L E Stearne
Department of Clincal Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
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I A Bakker-Woudenberg
Department of Clincal Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, The Netherlands.
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DOI: 10.1128/AAC.39.9.1954
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ABSTRACT

Pegylated amphotericin B (AmB) liposomes (PEG-AmB-LIP) were compared with laboratory-prepared nonpegylated AmB liposomes (AmB-LIP), a formulation with a lipid composition the same as that in AmBisome, as well as with industrially prepared AmBisome regarding their in vitro antifungal activities, toxicities, blood residence times, and therapeutic efficacies. Killing of Candida albicans (> 99.9%) during short-term (6-h) incubation was observed at 0.2 mg of AmB per liter for AmB desoxycholate, 0.4 mg of AmB per liter for PEG-AmB-LIP, 0.8 mg of AmB per liter for AmB-LIP, and 12.8 mg of AmB per liter for AmBisome. The maximum tolerated doses of PEG-AmB-LIP, AmB-LIP, and AmBisome were 15, 19, and > 31 mg of AmB per kg of body weight, respectively. In contrast to AmB-LIP, the blood residence time of PEG-AmB-LIP was prolonged and dose independent. In a model of systemic candidiasis in leukopenic mice at a dose of 5 mg of AmB per kg, PEG-AmB-LIP was completely effective and AmB-LIP was partially effective, whereas AmBisome was not effective. AmB-LIP at 11 mg of AmB per kg was partially effective. AmBisome at 29 mg of AmB per kg was completely effective. In conclusion, the therapeutic efficacies of AmB liposomes can be improved by preparing AmB liposomes in which a substantial reduction in toxicity is achieved while antifungal activity is retained. In addition, therapeutic efficacy is favored by a prolonged residence time of AmB liposomes in blood.

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Amphotericin B liposomes with prolonged circulation in blood: in vitro antifungal activity, toxicity, and efficacy in systemic candidiasis in leukopenic mice.
E W van Etten, M T ten Kate, L E Stearne, I A Bakker-Woudenberg
Antimicrobial Agents and Chemotherapy Sep 1995, 39 (9) 1954-1958; DOI: 10.1128/AAC.39.9.1954

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Amphotericin B liposomes with prolonged circulation in blood: in vitro antifungal activity, toxicity, and efficacy in systemic candidiasis in leukopenic mice.
E W van Etten, M T ten Kate, L E Stearne, I A Bakker-Woudenberg
Antimicrobial Agents and Chemotherapy Sep 1995, 39 (9) 1954-1958; DOI: 10.1128/AAC.39.9.1954
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