AEROSOLIZED AMBISOME TREATMENT OF PULMONARY CRYPTOCOCCUS-NEOFORMANS INFECTION IN MICE

AmBisome, a liposomal formulation of amphotericin B (ampB-lip), was te sted as an aerosol for delivery to the lungs for the treatment of pulm onary fungal diseases. AmBisome (4.6 mg of ampB/ml) was generated with an AeroTech II (AT) nebulizer, producing an aerosol during 20 of nebu lization of 111.3 mu g of ampB/L and with a mass median aerodynamic di ameter of 1.8 mu m. Antifungal activity of AmBisome was not affected b y 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 aerosolizat ion, there was a gradual loss of drug from the lungs. Multiple treatme nts 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 detec ted in lung tissue 14 days after treatment (24 mg/g). AmpB was not det ected in the blood. The prophylactic and therapeutic efficacy of aeros olized AmBisome in an intranasal Cryptococcus-mouse model was studied. Both the number of organisms colonizing the lungs and the gross lung scores were significantly reduced in all treated groups compared to co ntrols, whether treatment was begun before or after infection. Delayin g infection for 14 days after prophylactic treatment still was protect ive. Thus, AmBisome aerosol was effective in protecting mice from pulm onary cryptococcal infection.