In Vitro and In Vivo Activities of NS-718, a New Lipid Nanosphere Incorporating Amphotericin B, against Aspergillus fumigatus

Abstract

We evaluated the in vitro and in vivo potencies of a new lipid nanosphere that incorporates amphotericin B (AmB), NS-718, againstAspergillus fumigatus. The in vitro activity of NS-718 (the MIC at which 90% of strains are inhibited [MIC90], 0.25 μg/ml) against 18 isolates of A. fumigatus was similar to that of deoxycholate AmB (D-AmB; Fungizone; MIC90, 0.25 μg/ml), but NS-718 was more potent than liposomal AmB (L-AmB; AmBisome; MIC90, 1.0 μg/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 equivalent 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%). To explain these differences, pharmacokinetic studies showed higher concentrations 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 preparation of AmB, is a promising antifungal agent with activity against pulmonary aspergillosis.

Amphotericin B Formulations and Drug Targeting

“…85 Lipid nanospheres composed of soybean oil and purified egg yolk lecithin of 25-50 mm size have been proposed for the treatment of Aspergillus fumigatus infections in an experimental rat model. 89 The nanospheres were more effective for the treatment of invasive pulmonary aspergillosis than the Fungizone 1 and liposomal (AmBisome 1 ) AmB formulations.…”

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

“…Likewise, Zhao et al relevantly used a A. fumigatus strain that came from fungal endophthalmitis for their work about eye aspergillosis (Zhao et al, 2015). In contrast, it was more questionable when were used A. fumigatus strains that had not been isolated in a context of invasive aspergillosis, like MF13 first found in a sputum secondary to aspergilloma (Mitsutake et al, 1995; Otsubo et al, 1998, 1999; Kakeya et al, 2008; Takazono et al, 2009) or CBS 100079 in a human ear (Sarfati et al, 2002). Likewise, Af285 had been isolated from the sputum of a patient suffering from allergic aspergillosis, but not invasive form (Madan et al, 2001, 2010; Kaur et al, 2007; Singh et al, 2009).…”

Novel Drug Delivery Systems for Antifungal Compounds

“…NS-718 showed efficacy against pulmonary aspergillosis in rats and pulmonary cryptococcosis in mice. In vitro, the compound had similar activity against C. albicans, C. neoformans, and A. fumigatus, and was more effective against murine pulmonary cryptococcosis and aspergillosis than equimolar dosages of D-AmB and L-AmB (Hossain et al 1998;Maesaki et al 1999b;Otsubo et al 1999). In vitro, the compound had similar activity against C. albicans, C. neoformans, and A. fumigatus, and was more effective against murine pulmonary cryptococcosis and aspergillosis than equimolar dosages of D-AmB and L-AmB (Hossain et al 1998;Maesaki et al 1999b;Otsubo et al 1999).…”

“…The renal and nephrotic toxicity of NS-718 was estimated to be lower than that of AmB from the results of the toxicity study in the rat infusion model (Maesaki et al 1999a). NS-718 exhibited reduced uptake by the MPS, prolonged residence in the bloodstream and distribution to other extravascular sites, as evidenced by higher peak concentrations and area under the curve (AUC)-values in lung tissue (Otsubo et al 1999). NS-718 exhibited reduced uptake by the MPS, prolonged residence in the bloodstream and distribution to other extravascular sites, as evidenced by higher peak concentrations and area under the curve (AUC)-values in lung tissue (Otsubo et al 1999).…”