Efficacy of an oral lipid nanocrystal formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis

• Published in: Antimicrobial agents and chemotherapy 2024-04, Vol.68 (6), p.e0154023
• Main Authors: Gu, Yiyou, Gebremariam, Teclegiorgis, Alkhazraji, Sondus, Youssef, Eman, El-Gamal, Sabrina, Matkovits, Theresa, Cobb, Jenel, Mannino, Raphael, Ibrahim, Ashraf S
• Format: Article
• Language: English
• Subjects: Administration, Oral; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Animals; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Disease Models, Animal; Experimental Therapeutics; Female; Lung Diseases, Fungal - drug therapy; Lung Diseases, Fungal - microbiology; Mice; Mucor - drug effects; Mucormycosis - drug therapy; Mycology; Nanoparticles - chemistry; Neutropenia - drug therapy; Rhizopus - drug effects
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.01540-23

Invasive mucormycosis (IM) is associated with high mortality and morbidity. MAT2203 is an orally administered lipid nanocrystal formulation of amphotericin B, which has been shown to be safe and effective against other fungal infections. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to var. or DI15-131. In var. -infected mice, 15 mg/kg of MAT2203 qd was as effective as 10 mg/kg of LAMB in prolonging median survival time vs placebo (13.5 and 16.5 days for MAT2203 and LAMB, respectively, vs 9 days for placebo) and enhancing overall survival vs placebo-treated mice (40% and 45% for MAT2203 and LAMB, respectively, vs 0% for placebo). A higher dose of 45 mg/kg of MAT2203 was not well tolerated by mice and showed no benefit over placebo. Similar results were obtained with mice infected with . Furthermore, while both MAT2203 and LAMB treatment resulted in a significant reduction of ~1.0-2.0log and ~2.0-2.5log in or lung and brain burden vs placebo mice, respectively, LAMB significantly reduced tissue fungal burden in mice infected with vs tissues of mice treated with MAT2203. These results support continued investigation and development of MAT2203 as a novel and oral formulation of amphotericin for the treatment of mucormycosis.