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

NS-718, a lipid nanosphere incorporating amphotericin B, is effective again st pathogenic fungi and has low toxicity. We compared the toxicity of NS-71 8 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vit ro using renal cell cultures and in vivo by biochemical analysis, histopath ological study of the kidney and pharmacokinetic study of amphotericin B fo llowing 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 creatin ine 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. Histopatholog ical examination of the kidney showed tubular necrosis in D-AmB-treated rat s but no change in NS-718-treated rats. Amphotericin B concentrations in th e kidney in NS-718-treated rats were higher than those in D-AmB-treated rat s, Our in vitro and in vivo results suggest that Incorporation of amphoteri cin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amp hotericin B.