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Antimicrobial Agents and Chemotherapy, June 2000, p. 1463-1469, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Antifungal Activity of Amphotericin B Cochleates against Candida albicans Infection in a Mouse Model

Leila Zarif,1,* John R. Graybill,2 David Perlin,3 Laura Najvar,2 Rosie Bocanegra,2 and Raphael J. Mannino1

BioDelivery Sciences, Inc., UMDNJ, New Jersey Medical School, Newark, New Jersey 071031; University of Texas Health Science Center, San Antonio, Texas 782842; and Public Health Research Institute, New York, New York 100163

Received 22 November 1999/Returned for modification 3 January 2000/Accepted 10 March 2000

Cochleates are lipid-based supramolecular assemblies composed of natural products, negatively charged phospholipid, and a divalent cation. Cochleates can encapsulate amphotericin B (AmB), an important antifungal drug. AmB cochleates (CAMB) have a unique shape and the ability to target AmB to fungi. The minimal inhibitory concentration and the minimum lethal concentration against Candida albicans are similar to that for desoxycholate AmB (DAMB; Fungizone). In vitro, CAMB induced no hemolysis of human red blood cells at concentrations of as high as 500 µg of AmB/ml, and DAMB was highly hemolytic at 10 µg of AmB/ml. CAMB protect ICR mice infected with C. albicans when the agent is administered intraperitoneally at doses of as low as 0.1 mg/kg/day. In a tissue burden study, CAMB, DAMB, and AmBisome (liposomal AmB; LAMB) were effective in the kidneys, but in the spleen CAMB was more potent than DAMB at 1 mg/kg/day and was equivalent to LAMB at 10 mg/kg/day. In summary, CAMB are highly effective in treating murine candidiasis and compare well with AmBisome and AmB.

* Corresponding author. Mailing address: BioDelivery Sciences, Inc., UMDNJ, NJ Medical School, 185 South Orange Ave., Bldg. 4, Newark, NJ 07103. Phone: (973) 972-0324. Fax: (973) 972-0323. E-mail: zarifle{at}umdnj.edu.

Antimicrobial Agents and Chemotherapy, June 2000, p. 1463-1469, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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