Amphotericin B Lipid Complex (Ablc™): A Molecular Rationale for the Attenuation of Amphotericin B Related Toxicities

Abstract

Despite its associated toxicities, amphotericin B remains the drug of first choice for a variety of systemic fungal infections that were invariably fatal prior to its introduction. A natural product of Streptomyces, the structure of this compound is quite remarkable: it is approximately the length of a phospholipid molecule but possesses along its long axis both a polyhydroxyl and polyene hydrocarbon backbone. These domains of opposite polarity imbue amphotericin with unusual solubility properties, appear to be the key to its destruction of cells via membrane perturbation and depletion of transmembrane ion gradients, and have attracted, over the years, the attentions of a plethora of physical chemists interested in drug-lipid interactions. The association of amphotericin with liposome membranes has been studied extensively and has been related to lipid composition, radius of curvature, physical state, the amount and type of sterol present, and in our hands, drug/lipid ratios (1).