Abstract
A submicron amphotericin B (AmB) sterile emulsion with a mean droplet size of approximately 100 nm was prepared. The emulsion was stable at 4 degrees C over a period of 4 months. The acute toxicity results showed that the maximum tolerated dose of the AmB emulsion was 2.0 mg kg-1 as compared to 0.5 mg kg-1 for a commercial deoxycholate suspension, Fungizone. Efficacy evaluations of submicron AmB emulsion compared to Fungizone were performed in a murine candidiasis model using either a single or a multiple daily dose administration of 0.4 mg kg-1. Survival (100%) was observed up to 15-18 days post-infection in mice treated with AmB emulsion or Fungizone, while all control non-treated animals had died after 9 days in both single and multi-treatment experiments. Survival (50%) was obtained after 35 days in the single treatment, and 40 days in the multi-treatment, experiment with AmB emulsion, while treatment with Fungizone gave 50% survival after 15 and 20 days, respectively. The overall results indicate that in murine candidiasis, treatment with AmB submicron emulsion was more effective than Fungizone, suggesting a potential therapeutic application.
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