Liposomal amphotericin-B in the control of experimental aspergillosis in mice: Part I--Relative therapeutic efficacy of free and liposomal amphotericin-B.

ABSTRACT

An animal model system for aspergillosis in BALB/c mice has been developed to evaluate the therapeutic efficacy of liposomal Amphotericin-B (Amp-B) and commercial Amp-B (Fungizone). Amp-B was intercalated into liposomes composed of egg phosphatidylcholine, phosphatidylethanolamine and cholesterol in a molar ratio of 613. A single dose (0.5 mg/kg body wt) of Amp-B both alone as well as in liposomal preparation was injected (i.v.) into animals infected with Aspergillus fumigatus. An increase in survival rate of animals and decrease in fungal count in lung, the most affected organ, were observed with liposomal formulation. Inclusion of Amp-B into liposomes also reduced the toxicity of the drug. Tissue distribution analysis of Amp-B by HPLC showed an increase in concentration of the drug in lung for both free and liposomal Amp-B in infected animals as compared to normal. Use of liposomal Amp-B increased the concentration of the drug in the disease affected organs such as lung, spleen. A longer persistence of the drug in the infected organs was also observed. The results suggest that inclusion of Amp-B in liposomes decreases its toxicity and improves therapeutic efficacy which at least in part could be due to more deposition and longer persistence of the drug in infected tissues.