https://doi.org/10.3390/pharmaceutics14030671
Thomas Sécher1,2, Elsa Bodier-Montagutelli1,2,3,†, Christelle Parent1,2,†, Laura Bouvart1,2,4, Mélanie Cortes1,2, Marion Ferreira1,2,5, Ronan MacLoughlin6,7,8, Guy Ilango1,2, Otmar Schmid9, Renaud Respaud1,2,3, Nathalie Heuzé-Vourc’h1,2,*
1 INSERM, Centre d’Etude des Pathologies Respiratoires, U1100, F-37032 Tours, France
2 Faculté de Médecine, Université de Tours, F-37032 Tours, France
3 Service de Pharmacie, Centre Hospitalier Régional Universitaire de Tours, F-37032 Tours, France
4 Département de Médecine Pédiatrique, Centre Hospitalier Régional Universitaire de Tours, F-37032 Tours, France
5 Département de Pneumologie et d’Exploration Respiratoire Fonctionnelle, Centre Hospitalier Régional Universitaire de Tours, F-37032 Tours, France
6 Research and Development, Science and Emerging Technologies, Aerogen Limited, Galway Business Park, H91 HE94 Galway, Ireland
7 School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
8 School of Pharmacy and Pharmaceutical Sciences, Trinity College, D02 PN40 Dublin, Ireland
9 Institute of Lung Health and Immunology/Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), 85764 Munich, Germany
* Author to whom correspondence should be addressed.
† These authors contributed equally to this work.
Inhaled therapeutic antibodies offer a promising approach for treating respiratory diseases. This study demonstrates that antibodies can form aggregates during nebulization, triggering unwanted immune responses. Aerosolized IgG aggregates activate immune cells, promote inflammatory signals, and can even cause local and systemic immune cell loss in vivo. Importantly, these effects are specific to inhaled delivery and can be significantly reduced by improving antibody stability, for example through the addition of polysorbates.
The findings highlight the critical importance of careful formulation and the choice of an appropriate nebulizer to prevent pro-inflammatory and cytotoxic effects in inhalable antibody therapies.
