RT Journal Article T1 Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers A1 de Pablo, E A1 O'Connell, Peter A1 Fernández García, Raquel A1 Marchand, Sandrine A1 Chauzy, A. A1 Tewes, F A1 Dea Ayuela, María Auxiliadora A1 Kumar, D. A1 Bolas Fernández, Francisco A1 Ballesteros Papantonakis, María De La Paloma A1 Torrado Durán, Juan José A1 Healy, Anne Marie A1 Serrano López, Dolores Remedios AB The incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7% AmB with 39.7% γ-cyclodextrin, 8.1% mannose and 12.5% leucine. An increase in the mannose concentration from 8.1 to 29.8%, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80% FPF< 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water. PB Elsevier SN 0378-5173 YR 2023 FD 2023-03-25 LK https://hdl.handle.net/20.500.14352/73046 UL https://hdl.handle.net/20.500.14352/73046 LA eng NO Ministerio de Ciencia e Innovacion de España NO Science Foundation Ireland DS Docta Complutense RD 6 abr 2025