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Martini, N.* ; Deßloch, L.* ; Sych, T.* ; Berninghausen, O.* ; Merl-Pham, J. ; Dijkstra, S.* ; Carneiro, S.P.* ; Frankenberger, M. ; Beckmann, R.* ; Behr, J.* ; Matschiner, G.* ; Schuberth-Wagner, C.* ; Yildirim, A.Ö. ; Jürgens, D.C.* ; Sezgin, E.* ; Merkel, O.M.* ; Winkeljann, B.*

Understanding excipient interactions unlocks untapped potential of RNA-lipid nanoparticles in dry powder formulations for local pulmonary delivery.

J. Control. Release 390:114539 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Small interfering RNA (siRNA)-loaded lipid nanoparticles (LNPs) are a promising modality for gene silencing therapies. Pulmonary delivery offers an attractive, non-invasive route to target respiratory diseases. However, the development of stable dry powder formulations suitable for inhalation remains a key challenge. In this study, we investigated the impact of spray drying on the physicochemical integrity and biological performance of siRNA-LNPs. Four LNP formulations differing in PEG-lipid helper lipid content were subjected to spray drying in the presence of a lactose matrix. The impact of formulation parameters on physicochemical integrity, colloidal stability, structural preservation, and biological behaviour was systematically evaluated before and after spray drying and predicted by molecular dynamic simulations. Choosing this holistic approach demonstrates that LNP composition critically influences suitability for spray drying and provides key insights for the development of stable pulmonary siRNA therapies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Lipid Nanoparticles ; Lung Delivery ; Molecular Dynamic Simulation ; Mucus Diffusion ; Spray Drying; Gui-membrane-builder; Messenger-rna; Molecular-dynamics; Trehalose; Sirna; Hydration; Bilayer; Lung; Sucrose; Gromacs
ISSN (print) / ISBN 0168-3659
e-ISSN 1873-4995
Zeitschrift Journal of Controlled Release
Quellenangaben Band: 390, Heft: , Seiten: , Artikelnummer: 114539 Supplement: ,
Verlag Elsevier
Verlagsort Radarweg 29, 1043 Nx Amsterdam, Netherlands
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Institute of Lung Health and Immunity (LHI)
Förderungen Hevolution Foundation
European Research Council
Leibniz Supercomputing Centre
Swedish Research Council
Wellcome Leap's Dynamic Resilience Program - (Temasek Trust)
Karolinska Institutet
Cancer Research KI
Human Frontier Science Program
Longevity Impetus Grant from Norn Group
Rosenkranz Foundation
DFG