Journal Article

Low nephrotoxicity of an effective amphotericin B formulation with cationic bilayer fragments

Nilton Lincopan, Elsa M. Mamizuka and Ana M. Carmona-Ribeiro

in Journal of Antimicrobial Chemotherapy

Volume 55, issue 5, pages 727-734
Published in print May 2005 | ISSN: 0305-7453
Published online May 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki064
Low nephrotoxicity of an effective amphotericin B formulation with cationic bilayer fragments

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  • Medical Oncology
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Objectives: Evaluation of nephrotoxicity of a novel amphotericin B (AMB) formulation with dioctadecyldimethylammonium bromide (DODAB) bilayer fragments (DOD/AMB).

Methods: Dose-dependent cytotoxicity of DOD/AMB was evaluated in vitro against cultured kidney epithelial cells in culture. For in vivo experiments, Swiss Webster female mice were injected intraperitoneally for 10 consecutive days with 0.4 mg/kg/day AMB in the form of traditional bile salt desoxycholate (DOC)/AMB or DOD/AMB. Body and spleen weight, and biochemical and histopathological data were obtained at days 11 and 180 after injection.

Results: Nephrotoxicity of the novel formulation was lower than that of Fungizone (DOC/AMB), which is the traditional AMB formulation using DOC. Dose-dependent cytotoxicity of DOD/AMB was lower than that exhibited by DOC/AMB. At day 11, DODAB and DOD/AMB caused loss of body weight and increase in spleen weight, which were not observed for DOC/AMB, although the changes were reversible and weights returned to control values at day 180. Ten days after injection, biochemical parameters for hepatic and renal function remained unaltered. At day 180, renal cortex histopathology revealed leucocytic infiltration and moderate hydropic degeneration of the renal tubules in the DODAB and DOD/AMB groups, in contrast to more severe lesions observed for the DOC/AMB group such as tubular cystic degeneration and glomerular injury, which were absent for the former groups.

Conclusions: The DOD/AMB formulation exhibited differential cytotoxicity and low nephrotoxicity, but there were also important aspects of general toxicity that will require evaluation with full-scale toxicity protocols.

Keywords: dioctadecyldimethylammonium bromide; cytotoxicity; renal function; histopathology

Journal Article.  5337 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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