Chemotherapeutic activity of liposomal SJA-95: a new polyene macrolide antibiotic in experimental aspergillosis and cryptococcosis.
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.
Department of Pharmacology, Prin. K.M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai, India.
Sandhya K
SK
Desai
Suresh R
SR
Naik
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000302:isolation & purification; D001921:Brain / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy*; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000302:isolation & purification; D004353:Drug Evaluation, Preclinical; D016469:Fungemia / Q000188:drug therapy*; D007668:Kidney / Q000382:microbiology; D007928:Lethal Dose 50; D007958:Leukocyte Count; D008081:Liposomes / Q000008:administration & dosage; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D018942:Macrolides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D011090:Polyenes / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D013154:Spleen / Q000382:microbiology
D000935:Antifungal Agents; D008081:Liposomes; D018942:Macrolides; D011090:Polyenes; C519970:SJA-95