Preparation, relative toxicity and therapeutic efficacy in mice and rats of liposomal HA-1-92, a new oxohexaene polyene macrolide antibiotic.
HA-1-92, a new polyene oxohexaene macrolide antibiotic isolated from Streptomyces CDRIL-312, was incorporated into liposomes containing phosphotidyl choline and cholesterol. The liposomal incorporated HA-1-92 considerably decreased toxicity when compared with free HA-1-92 in mice. Liposomal HA-1-92 showed improved pharmacokinetic profiles in rats. When administered to aspergillosis- and cryptococcosis-infected Balb/c mice, liposomal HA-1-92 showed increased antifungal activity, compared with free HA-1-92, with improved survival rate and decreased colony-forming units in lung, liver, spleen and kidney. These results suggest that liposomal HA-1-92 is more effective than free HA-1-92 in controlling experimental aspergillosis and cryptococcosis in Ba1b/c mice.
Harindran
J
J
Research and Development Division, Hindustan Antibiotics Ltd, Pimpri, Pune, India.
Chakraborty
K K
KK
Naik
S R
SR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D001232:Aspergillus fumigatus / Q000187:drug effects; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D003455:Cryptococcus neoformans / Q000187:drug effects; D005260:Female; D006207:Half-Life; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D008081:Liposomes / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000382:microbiology; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology; D018942:Macrolides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009129:Muscle Tonus / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012120:Respiration Disorders / Q000139:chemically induced; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D015996:Survival Rate; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; C121411:HA-1-92; D008081:Liposomes; D018942:Macrolides