Antifungal activity of amphotericin B cochleates against Candida albicans infection in a mouse model.
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 microg of AmB/ml, and DAMB was highly hemolytic at 10 microg 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.
Zarif
L
L
BioDelivery Sciences, Inc., UMDNJ, New Jersey Medical School, Newark, New Jersey 07103, USA. zarifle@umdnj.edu
Graybill
J R
JR
Perlin
D
D
Najvar
L
L
Bocanegra
R
R
Mannino
R J
RJ
D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D006801:Humans; D051379:Mice
D000935:Antifungal Agents; D000666:Amphotericin B