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. 2023 Mar 25:635:122788.
doi: 10.1016/j.ijpharm.2023.122788. Epub 2023 Mar 1.

Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers

E de Pablo  1 , P O'Connell  2 , R Fernández-García  1 , S Marchand  3 , A Chauzy  4 , F Tewes  3 , M A Dea-Ayuela  5 , D Kumar  6 , F Bolás  7 , M P Ballesteros  8 , J J Torrado  8 , A M Healy  2 , D R Serrano  9
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Free article

Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers

E de Pablo et al. Int J Pharm. .
Free article

Abstract

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.

Keywords: ASAP; Amorphous; Amphotericin B; Crystalline; Dry powder inhaler; Pulmonary administration; Spray drying.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.