Efficacy of oral cochleate-amphotericin B in a mouse model of systemic candidiasis

Amphotericin B (AMB) remains the principal therapeutic choice for deep myco ses. However, its application is limited by toxicity and a route of adminis tration requiring slow intravenous injection, An oral formulation of this d rug is desirable to treat acute infections and provide prophylactic therapy for high-risk patients. Cochleates are a novel lipid-based delivery system that have the potential for oral administration of hydrophobic drugs. They are stable phospholipid-cation crystalline structures consisting of a spir al lipid bilayer sheet with no internal aqueous space. Cochleates containin g AMB (CAMB) inhibit the growth of Candida albicans, and the in vivo therap eutic efficacy of CAME administered orally was evaluated in a mouse model o f systemic candidiasis. The results indicate that 100% of the mice treated at all CAMB doses, including a low dosage of 0.5 mg/kg of body weight/day, survived the experimental period (16 days). In contrast, 100% mortality was observed with untreated mice by day 12. The fungal tissue burden in kidney s and lungs was assessed in parallel, and a dose-dependent reduction in C. albicans from the kidneys was observed, with a maximum 3.5-log reduction in total cell counts at 2.5 mg/kg/day. However, complete clearance of the org anism from the lungs, resulting in more than a 4-log reduction, was observe d at the same dose. These results were comparable to a deoxycholate AMB for mulation administered intraperitoneally at 2 mg/kg/day (P < 0.05). Overall, these data demonstrate that cochleates are an effective oral delivery syst em for AMB in a model of systemic candidiasis.