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Understanding excipient interactions unlocks untapped potential of RNA-lipid nanoparticles in dry powder formulations for local pulmonary delivery.
J. Control. Release, DOI: 10.1016/j.jconrel.2025.114539:114539 (2025)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Lipid Nanoparticles ; Lung Delivery ; Molecular Dynamic Simulation ; Mucus Diffusion ; Spray Drying
ISSN (print) / ISBN
0168-3659
e-ISSN
1873-4995
Journal
Journal of Controlled Release
Quellenangaben
Article Number: 114539
Publisher
Elsevier
Reviewing status
Peer reviewed