Preclinical & pharmaceutical testing of liposomal amphotericin B.

ABSTRACT

Various liposomal amphotericin-B formulations prepared from soya phosphatidylcholine and cholesterol were tested for toxicity, therapeutic efficacy and stability in mice infected with Aspergillus fumigatus. No advantage was noted by removing the unencapsulated drug from that bound to liposomes, as evident by the LD50 and efficacy being similar with both dialyzed and undialyzed formulations. Small unilamellar liposomes were more effective and less toxic, but also less stable, as compared to multilamellar vesicles. In view of these results, multilamellar liposomes were prepared without removing the unencapsulated drug and converted to unilamellar vesicles just prior to administration. The LD50 and efficacy of this formulation was similar to freshly prepared small unilamellar liposomes. These liposomes were prepared under aseptic conditions and were found to be sterile and pyrogen-free. The batch-to-batch variation was also found to be quite low, and therefore liposomal amphotericin B formulation suitable for administration in patients suffering with systemic fungal infection has been developed.