Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B.

Abstract

NS-718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS-718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D-AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D-AmB 3 mg/kg but not in those given the same dose of NS-718. Histopathological examination of the kidney showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amphotericin B.

Journal

Journal ID (iso-abbrev): J. Antimicrob. Chemother.

Title: The Journal of antimicrobial chemotherapy

ISSN: 0305-7453

ISSN (Print): 0305-7453

Publication date (Electronic): Aug 2000

Volume: 46

Issue: 2

Affiliations

[1 ] Second Department of Internal Medicine and Second Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.

Article

PubMed ID: 10933650