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.
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 x 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.
Brime
Begoña
B
Department of Pharmacy and Pharmaceutical Technology, Complutense University of Madrid, 28040 Madrid, Spain.
Molero
Gloria
G
Frutos
Paloma
P
Frutos
Gloria
G
D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002177:Candidiasis / Q000188:drug therapy* / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D003840:Deoxycholic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004655:Emulsions; D005612:Freeze Drying; D007121:Immunocompetence / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009503:Neutropenia / Q000188:drug therapy* / Q000276:immunology; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D004655:Emulsions; D010713:Phosphatidylcholines; D003840:Deoxycholic Acid; D000666:Amphotericin B