Long-circulating immunoliposomal amphotericin B against invasive pulmonary aspergillosis in mice.
We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number of Aspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 microg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 microg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.
Otsubo
T
T
Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Maruyama
K
K
Maesaki
S
S
Miyazaki
Y
Y
Tanaka
E
E
Takizawa
T
T
Moribe
K
K
Tomono
K
K
Tashiro
T
T
Kohno
S
S
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis
D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B