Cochleates containing amphotericin B (CAMB) were administered orally at doses ranging from 0 to 40 mg/kg of body weight/day for 14 days in a murine model of systemic aspergillosis. The administration of oral doses of CAMB (20 and 40 mg/kg/day) resulted in a survival rate of 70% and a reduction in colony counts of more than 2 logs in lungs, livers, and kidneys. Orally administered CAMB shows promise for the treatment of aspergillosis.Aspergillus fumigatus causes a variety of diseases, including allergic bronchopulmonary aspergillosis in asthma patients and invasive pulmonary aspergillosis in immunocompromised patients (1, 7). Invasive pulmonary aspergillosis can be treated with broad-spectrum triazoles (2, 14) and echinocandins (14), yet amphotericin B (AmB) therapy remains the preferred treatment for severe Aspergillus infections (12). Unlike other classes of antifungals, AmB is highly toxic and shows poor oral bioavailability. In order to increase the therapeutic index of AmB, new lipid-based formulations have been developed (4,5,8). Despite improvement in the therapeutic index for liposomal AmB formulations, the overall prognosis for patients with invasive disease remains poor. Recently, cochleate delivery vehicles for amphotericin B have been introduced as a new platform for overcoming the poor oral bioavailability of AmB (9,16,17). It has been shown that orally administered cochleates containing amphotericin B (CAMB) were as effective as intraperitoneally (i.p.) administered deoxycholate AmB (DAMB) in protecting against mortality and reducing the fungal burden of tissues in a murine model of candidiasis (9). In this paper, we describe the efficacy in vivo of CAMB delivered orally in a mouse model of systemic aspergillosis.CAMB were prepared by use of an aqueous/aqueous hydrogel binary system (9) and produced an MIC of Ͻ1 g/ml for A. fumigatus challenge strain MSKCC R21 when tested in RPMI 1640 medium according to NCCLS protocol M38-P. CAMB were evaluated in a systemic aspergillosis model adapted from that described by Verweij and colleagues (13). Female BALB/c mice (20 to 22 g) were rendered susceptible to A. fumigatus infection by treatment with cyclophosphamide at 150 to 200 mg/kg of body weight via intravenous injection through the lateral tail vein 3 days prior to infection with 0.1 ml of saline containing 10 6 spores of A. fumigatus (MSKCC R21). Treatment was initiated immediately after infection by oral administration of CAMB for 14 days at 0 to 20 mg/kg/day for the group treated with 150 mg of cyclophosphamide/kg and at 0 to 40 mg/kg/day for the group treated with 200 mg of cyclophosphamide/kg. DAMB administered i.p. at 4 mg/kg/day was used as a positive control. Survival rates and tissue burden (CFU per gram) in kidneys, livers, and lungs were determined for each treatment.The efficacy in vivo of orally administered CAMB was evaluated in two separate trials of the disseminated aspergillosis model in which mice (10 per group) were treated daily for 14 days. In trial 1 (Fig. 1A), immunosuppression was ...