Chemotherapeutic activity of liposomal SJA-95: a new polyene macrolide antibiotic in experimental aspergillosis and cryptococcosis.

摘要

The incidence of systemic fungal infections that has risen dramatically over the past three decades has propelled a continuous need for more potent antifungal drugs. The purpose of this research was to evaluate the chemotherapeutic activity of a new heptaene polyene macrolide antibiotic (SJA-95) and liposomal incorporated SJA-95 (lip. SJA-95) in a mouse model of aspergillosis and cryptococcosis respectively. Lip. SJA-95 was prepared in our laboratory by the proliposome method involving incorporation of the antifungal into the proliposome mixture and its subsequent conversion into a liposomal dispersion by a simple dilution step. Treatment with free SJA-95 and lip. SJA-95, both in aspergillosis and cryptococcosis, progressively prolonged the survival time and decreased the fungal loads in vital organs respectively. A higher LD(50) value of lip. SJA as compared to that of free SJA-95 was indicative of reduced toxicity of lip. SJA-95. Our findings suggest lip. SJA-95 treatment results in prolonged survival time, effective microbiological clearance and reduced toxicity that might help to establish its usefulness as a chemotherapeutic agent in systemic fungal infections with fewer adverse reactions.