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Updated: Jan 8, 2026

Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
Understanding excipient interactions unlocks untapped potential of RNA-lipid nanoparticles in dry powder formulations
Nora Martini1, Leonie Deßloch2, Taras Sych3
1Department of Pharmacy, Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research (DZL), 81377 Munich, Germany.
Abstract:
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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