Cochleates are a novel lipid-based delivery vehicle consisting of phospholipid-cation crystalline structures that form spiral lipid sheets with little or no internal aqueous space. They represent a new technology platform for oral delivery of clinically important drugs that possess poor oral bioavailabilily (1-3). Cochleates containing AmB (CAMB) were administered orally (PO) from 0-40 mg/kg/day for 15 days in a murine model of systemic aspergillosis in which mice were rendered immunosuppressed with >=150 mg/kg cyclophosphamide. Tissue burden and survival were evaluated relative to Fungizone (DAME) administered by parenteral injection (IP) at 4 mg/kg/day. Dose-dependent protection was observed in the aspergillosis model with CAMB at 20 mg/kg/day, showing equivalent behavior with IP delivered DAMB at 4 mg/kg/day. Oral doses of 20-40 mg/kg/day CAMB showed 70% survival in the aspergillosis model and more than a two log reduction in CFU in lungs, liver and kidneys. Oral administration of CAMB showed promising results in the treatment of systemic aspergillosis in a murine infection model. Cochleate technology is an important new approach for oral delivery of amphotericin B.
Full conference title:
Focus on Fungal Infections 11, March 14-16 2001
- Focus on Fungal Infection 11 (2001)