Altered tissue distribution of amphotericin B by liposomal encapsulation: comparison of normal mice to mice infected with Candida albicans.

Abstract

Recently, it has been observed that encapsulation of Amphotericin B (Amp-B) into multilamellar vesicles (liposomes) decreases the toxicity associated with the administration of Amp-B, while maintaining its antifungal efficacy. In this study, the tissue concentrations of Amp-B in normal mice and in mice infected with Candida albicans were examined. Amp-B concentrations in various tissues were quantitated by high-performance liquid chromatography. Liposomal encapsulation improved the delivery of Amp-B to the liver, spleen, lung, and kidney in both normal and infected mice. Furthermore, after injection of the encapsulated drug, Amp-B was demonstrable in brain tissue of infected animals at potentially therapeutic concentrations. None was demonstrable in the brains of normal animals or animals injected with free Amp-B. The results suggest that capillary endothelial damage and phagocytic cell uptake may contribute to an enhanced liposome delivery of Amp-B to those organs most frequently infected with fungi.