Comparative therapeutic efficacy of a novel lyophilized amphotericin B lecithin-based oil?water microemulsion and deoxycholate-amphotericin B in immunocompetent and neutropenic mice infected with Candida albicans

Comparative therapeutic efficacy of a novel lyophilized amphotericin B lecithin-based oil?water microemulsion and deoxycholate-amphotericin B in immunocompetent and neutropenic mice infected with Candida albicans
August 2004
Bego?a Brimea, 1, Gloria Molerob, Paloma Frutosa and Gloria Frutos
European Journal of Pharmaceutical Sciences
Abstract
The in vivo efficacy of a new amphotericin B (AmB) oil-in-water lecithin-based microemulsion delivery system (M-AmB) compared to deoxycholate-AmB (D-AmB) was studied in an immunocompetent and neutropenic murine model of systemic candidiasis. D-AmB was administered at the maximum tolerated dose of 1 mg/kg whereas M-AmB was given at the doses of 1, 2 and 3 mg/kg; doses were well tolerated due to their reduced toxicity. Both formulations were administered 24, 48 and 72 h after infection in immunocompetent mice, and 2, 6 and 24 h after infection in neutropenic mice. Kaplan?Meier survival curves showed that the M-AmB treated group had a better survival time than infected mice without treatment used as a control group (P = 4.66 ? 10-6), and the Mann?Whitney W statistical test indicated that it reduced the percentage of mortality and fungal load in the most representative organs. This new formulation is a designed competitor which has proved to present better results than D-AmB in an established infection not only in immunocompetent but in neutropenic mice as well.