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Antimicrobial Agents and Chemotherapy, January 1998, p. 40-44, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Long-Circulating Immunoliposomal Amphotericin B against Invasive Pulmonary Aspergillosis in Mice

Takakazu Otsubo,1 Kazuo Maruyama,2 Shigefumi Maesaki,1 Yoshitsugu Miyazaki,1 Eitaro Tanaka,2 Tomoko Takizawa,2 Kunikazu Moribe,2 Kazunori Tomono,1 Takayoshi Tashiro,1 and Shigeru Kohno1,*

Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852,1 and Faculty of Pharmaceutical Science, Teikyo University, Sagamiko, Kanagawa 199-01,2 Japan

Received 6 June 1997/Returned for modification 21 July 1997/Accepted 17 October 1997

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 µg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 µg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.

* Corresponding author. Mailing address: Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto 1-7-1, Nagasaki 852, Japan. Phone: 81-95-849-7271. Fax: 81-95-849-7285. E-mail: sk1227{at}net.nagasaki-u.ac.jp.

Antimicrobial Agents and Chemotherapy, January 1998, p. 40-44, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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