In vitro and in vivo activities of NS-718, a new lipid nanosphere incorporating amphotericin B, against Aspergillus fumigatus

We evaluated the in vitro and in vivo potencies of a new lipid nanosphere t hat incorporates amphotericin B (AmB), NS-718, against Aspergillus fumigatu s. The in vitro activity of NS-718 (the MIC at which 90% of strains are inh ibited [MIC90], 0.25 mu g/ml) against 18 isolates of A. fumigatus was simil ar to that of deoxycholate AmB (D-AmB; Fungizone; MIC90, 0.25 mu g/ml), but NS-718 was more potent than liposomal AmB (L-AmB; AmBisome; MIC90, 1.0 mu g/ml). The in vivo efficacy of NS-718 in a rat model of invasive pulmonary aspergillosis was compared with those of D-AmB and L-AmB. A low dose (1 mg/ kg of body weight) of L-AmB was ineffective (survival rate, 0%), although e quivalent doses of D-AmB and NS-718 were more effective (survival rate, 17% ). However, a higher dose of NS-718 (3 mg/kg) was more effective (survival rate, 100%) than equivalent doses of D-AmB and L-AmB (survival rate, 0%). T o explain these differences, pharmacokinetic studies showed higher concentr ations of AmB in the plasma of rats treated with NS-718 than in the plasma of those treated with D-AmB. Our results suggest that NS-718, a new prepara tion of AmB, is a promising antifungal agent with activity against pulmonar y aspergillosis.