Mannosylated Liposome-Mediated Delivery of Amphotericin-B in the Control of Experimental Aspergillosis in BALB/c Mice.

Abstract

The effect of mannose grafting to the surface of Amphotericin B (Amp-B)-containing liposomes with and without cholesterol on the toxicity, therapeutic efficacy, and altered tissue distribution was studied in normal and infected mice. The inclusion of cholesterol in the mannose-grafted liposomes bearing Amp-B increased the LD50 from 8.4mg/kg to 20.3mg/kg body weight. Cholesterol was found to enhance the therapeutic efficacy of mannosylated liposomes. The tissue distribution studies indicated that incorporation of cholesterol in mannose-grafted liposomal formulation of Amp-B increased the tissue concentration in various organs of both healthy and infected mice. A significant increase in concentration of Amp-B in the lungs of infected animals was observed when mannosylated liposomes having cholesterol were administered. Inhibition of mannosylated liposomal formulation of Amp-B by mannan was observed in normal animals, but in infected animals there was no inhibition.