Aerosolized AmBisome Treatment of Pulmonary Cryptococcus neoformans Infection in Mice

Abstract

ABSTRACT AmBisome, a liposomal formulation of amphotericin B (ampB-lip), was tested as an aerosol for delivery to the lungs for the treatment of pulmonary fungal diseases. AmBisome (4.6 mg of ampB/ml) was generated with an AeroTech II (AT) nebulizer, producing an aerosol during 20 of nebulization of 111.3 μg of ampB/L and with a mass median aerodynamic diameter of 1.8 μm. Antifungal activity of AmBisome was not affected by aerosolization. When mice were treated with aerosolized AmBisome(4.5 mg of ampB/ml) every other day for a total of 3 treatments (0.6 mg/kg/20 min), lungs rapidly accumulated ampB. Some hours after aerosolization, there was a gradual loss of drug from the lungs. Multiple treatments led to an accumulation of ampB with a maximum concentration after the third treatment of 43 mg of ampB/gm of lung tissue. AmpB was detected in lung tissue 14 days after treatment (24 mg/g). AmpB was not detected in the blood. The prophylactic and therapeutic efficacy of aerosolized AmBisome in an intranasal Cr...