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Long-circulating immunoliposomal amphotericin B against invasive pulmonary aspergillosis in mice
T Otsubo1, K Maruyama, S Maesaki
1Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Abstract:
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.
Insights
Long-circulating immunoliposomal amphotericin B (34A-PEG-L-AmB) significantly improved survival rates in mice with invasive pulmonary aspergillosis. This novel formulation demonstrated superior efficacy compared to conventional and PEGylated liposomal amphotericin B.
Area of Science:
- Mycology
- Pharmacology
- Immunology
Background:
- Invasive pulmonary aspergillosis is a severe fungal infection with high mortality.
- Conventional amphotericin B formulations have limitations in efficacy and toxicity.
- Liposomal formulations aim to improve drug delivery and reduce side effects.
Purpose of the Study:
- To evaluate the efficacy of long-circulating immunoliposomal amphotericin B (34A-PEG-L-AmB) against invasive pulmonary aspergillosis in a murine model.
- To compare the efficacy of 34A-PEG-L-AmB with conventional liposomal amphotericin B (AmBisome) and polyethylene glycol-coated liposomal amphotericin B (PEG-L-AmB).
Main Methods:
- Murine model of invasive pulmonary aspergillosis.
- Treatment with intravenous doses of AmBisome, PEG-L-AmB, and 34A-PEG-L-AmB (2 mg/kg).
- Assessment of survival rates, fungal burden in lungs, and pharmacokinetic profiles.
Main Results:
- Survival rates were 16.7% for AmBisome, 83.3% for PEG-L-AmB, and 100% for 34A-PEG-L-AmB.
- 34A-PEG-L-AmB treatment resulted in a significant reduction in Aspergillus fumigatus in the lungs.
- Pharmacokinetic studies revealed high amphotericin B concentrations in plasma (PEG-L-AmB) and lungs (34A-PEG-L-AmB).
Conclusions:
- Long-circulating immunoliposomal amphotericin B (34A-PEG-L-AmB) is highly effective against invasive pulmonary aspergillosis in mice.
- 34A-PEG-L-AmB offers a promising therapeutic strategy for invasive aspergillosis.
- Targeted delivery and prolonged circulation contribute to the enhanced efficacy of 34A-PEG-L-AmB.