Development, Characterization, Efficacy and Mode of Action of Ambisome, A Unilamellar Liposomal Formulation of Amphotericin B

Abstract

AmBisome is a lyophilized formulation of amphotericin B incorporated into small unilamellar liposomes composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol, and cholesterol. In aqueous solution AmBisome is quite stable; less than 5% of the drug dissociates from the liposomes during a 72 hour incubation period in human plasma. This stability to loss of drug is a key factor, accounting for the ability of AmBisome to markedly reduce the well known acute and chronic toxicities associated with administration of amphotericin B. Numerous animal and clinical studies have documented therapeutic efficacy of AmBisome for a wide range of fungal infections. Mechanism of action studies indicate that AmBisome liposomes specifically bind to the fungal cell surface, dam the cell membrane, and kill the fungus. In some cases, AmBisome had a slightly lower potency than amphotericin B itself, but much higher doses of AmBisome could be administered safely resulting in an improved therapeutic profile.