Antifungal activity of amphotericin B cochleates against Candida albicans infection in a mouse model

Leila Zarif, John R. Graybill, David Perlin, Laura Najvar, Rosie Bocanegra, Raphael J. Mannino

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1463-1469
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume44
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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