Open AccessEfficacy of Oral Cochleate-Amphotericin B in a Mouse Model of Systemic Candidiasis
Author(s) -
Rosaria Santangelo,
Padmaja Paderu,
Guillaume Delmas,
Zi Wei Chen,
Raphael J. Mannino,
Leila Zarif,
David S. Perlin
Publication year - 2000
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.44.9.2356-2360.2000
Subject(s) - amphotericin b , oral administration , pharmacology , systemic candidiasis , candida albicans , in vivo , medicine , toxicity , drug , corpus albicans , therapeutic index , pharmacokinetics , pharmacodynamics , route of administration , biology , antifungal , microbiology and biotechnology , dermatology
Amphotericin B (AMB) remains the principal therapeutic choice for deep mycoses. However, its application is limited by toxicity and a route of administration requiring slow intravenous injection. An oral formulation of this drug 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 spiral lipid bilayer sheet with no internal aqueous space. Cochleates containing AMB (CAMB) inhibit the growth ofCandida albicans , and the in vivo therapeutic efficacy of CAMB administered orally was evaluated in a mouse model of 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 kidneys and lungs was assessed in parallel, and a dose-dependent reduction inC. 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 organism from the lungs, resulting in more than a 4-log reduction, was observed at the same dose. These results were comparable to a deoxycholate AMB formulation administered intraperitoneally at 2 mg/kg/day (P < 0.05). Overall, these data demonstrate that cochleates are an effective oral delivery system for AMB in a model of systemic candidiasis.