Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B.
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.
Hossain
M A
MA
Second Department of Internal Medicine and Second Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
Maesaki
S
S
Razzaque
M S
MS
Tomono
K
K
Taguchi
T
T
Kohno
S
S
D000410:Alanine Transaminase / Q000097:blood; D000666:Amphotericin B / Q000008:administration & dosage* / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D004337:Drug Carriers; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008863:Microspheres; D051381:Rats
D000935:Antifungal Agents; D004337:Drug Carriers; D000666:Amphotericin B; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase