Treatment of murine candidosis and cryptococcosis with a unilamellar liposomal amphotericin B formulation (AmBisome)

This investigation examined the therapeutic efficacy of AmBisome, a unilamellar (55–75 nm) liposome amphotcricin B preparation with a murine LD50 by the intravenous route of greater than 175 mg/kg amphotericin B. Both fungal burden and survival were used to evaluate the drug's efficacy against murine candidosis and cryptococcosis. Single and multiple dose intravenous treatment with AmBisome (2·5.5·0 and 10·0 mg/kg) reduced the colony forming units/mg kidney in candida-infected mice by 99% and improved survival by at kast 40% relative to untreated control mice. Repeated intravenous dosing of candida-infected mice with equivalent amounts (0·75 mg/kg) of conventional amphotericin B (Fungizone) or AmBisome showed comparable reduction of yeasts in the kidneys. When mice were infected syetemically with Cryptococcus neoformans, all but one of the 30 mice given AmBisome (5·0, 7·5 or 10·0 mg/kg) survived until the experiment was terminated 35 days after infection. Liver and spleen cultures from AmBisome-treated mice were negative for fungal growth. All the mice given conventional amphotericin B intraperitoneally at 4·5 mg/kg; survived and cleared the infection from the livers although some of the mice had infected spleens. The percentage of cultured brains free of cryptococcosis was 89% following treatment with 10·0 mg/kg AmBisome, and 80% with 4·5 mg/kg conventional drug. These preclinical studies of systemic candidosis and cryptococcosis demonstrate comparable efficacy of AmBisome and conventional arnphotericin B at low doses and improved efficacy with AmBisome at doses higher than can be safely administered of the conventional drug.