Efficacy evaluation of a novel submicron amphotericin B emulsion in murine candidiasis.
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.
Levy
M Y
MY
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Polacheck
I
I
Barenholz
Y
Y
Benita
S
S
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D003840:Deoxycholic Acid; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005069:Evaluation Studies as Topic; D005500:Follow-Up Studies; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016896:Treatment Outcome
D004655:Emulsions; D003840:Deoxycholic Acid; D000666:Amphotericin B