PRECLINICAL AND PHARMACEUTICAL TESTING OF LIPOSOMAL AMPHOTERICIN-B

Various liposomal amphotericin-B formulations prepared from soya phosp hatidylcholine and cholesterol were tested for toxicity, therapeutic e fficacy and stability in mice infected with Aspergillus fumigatus. No advantage was noted by removing the unencapsulated drug from that boun d to liposomes, as evident by the LD50 and efficacy being similar with both dialyzed and undialyzed formulations. Small unilamellar liposome s were more effective and less toxic, but also less stable, as compare d to multilamellar vesicles. In view of these results, multilamellar l iposomes were prepared without removing the unencapsulated drug and co nverted to unilamellar vesicles just prior to administration. The LD50 and efficacy of this formulation was similar to freshly prepared smal l unilamellar liposomes. These liposomes were prepared under aseptic c onditions and were found to be sterile and pyrogen-free. The batch-to- batch variation was also found to be quite low, and therefore liposoma l amphotericin B formulation suitable for administration in patients s uffering with systemic fungal infection has been developed.