title: Efficient treatment of murine systemic infection with Candida albicans using amphotericin B incorporated in nanosize range particles (emulsomes).
abstract: The effects of emulsome nanosize range lipid particles containing amphotericin B (EAmB) were compared with the reference formulation containing deoxycholate (Fungizone; Bristol-Myers Squibb, Munich, Germany) and with the commercial amphotericin lipid complex preparation (AmBisome; Nexstar, San Dimas, CA, USA). The minimal inhibitory concentrations of Fungizone and EAmB were identical although killing of Candida albicans was delayed when EAmB was used. In a tissue culture model and in mice, the incorporation of AmB into emulsomes resulted in a considerable reduction of toxicity in comparison with Fungizone. For comparison of the in vivo effect of the preparations a mouse model of systemic infection with C. albicans was used. All preparations were able to reduce the fungal burden in the liver and kidneys in comparison with control animals treated with isotonic saline. AmBisome was more efficient in the reduction of the fungal burden of the liver than EAmB and Fungizone, even when applied in a similar dosage of 1 mg kg(-1). In the kidneys, EAmB and Fungizone was slightly more effective than AmBisome. Therefore, in our models, the incorporation of AmB into nanosize particles was able to reduce toxicity without loss of efficiency. EAmB may be considered a candidate preparation for the treatment of infections with C. albicans in humans.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kretschmar
authors.forename: S
authors.initials: S
authors.lastname: Amselem
authors.forename: E
authors.initials: E
authors.lastname: Zawoznik
authors.forename: K
authors.initials: K
authors.lastname: Mosbach
authors.forename: A
authors.initials: A
authors.lastname: Dietz
authors.forename: H
authors.initials: H
authors.lastname: Hof
authors.forename: T
authors.initials: T
authors.lastname: Nichterlein
mesh_terms: D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D018929:Cell Culture Techniques; D005260:Female; D016469:Fungemia / Q000188:drug therapy* / Q000382:microbiology; D007378:Interleukins / Q000378:metabolism; D008055:Lipids; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013535:Suspensions; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D007378:Interleukins; D008055:Lipids; D008081:Liposomes; D013535:Suspensions; D000666:Amphotericin B