ISIS Neutron and Muon Source Data Journal

Using SANS to Probe Structural Changes of RNA Lipid Nanoparticles in Spray Dried Powder for Pulmonary Delivery

Abstract: RNA therapeutics holds significant promise for treating lung diseases, but their clinical application is limited by the lack of efficient delivery system suitable for inhalation. Dry powder inhaler (DPI) formulation is appealing due to its excellent stability. Lipid nanoparticles (LNPs) are widely studied RNA delivery platform yet their use in pulmonary delivery remains challenging. Aerosolisation and drying process can perturb lipid organisation, leading to aggregation or structural disruption, thereby compromising delivery efficiency. Small angle neutron scattering (SANS) offers a powerful approach to elucidate the internal structural changes of lipid systems under such conditions. Here, we will employ spray drying technique to produce DPI formulations using various stabilising excipients to maintain LNP integrity. This study builds upon our optimised RNA LNP formulations by employing PEG-alternative steric lipids that demonstrated excellent stability during nebulisation while successfully preserving RNA transfection efficiency. Using SANS with contrast matching approach, the structural characteristics of spray-dried LNP formulations upon rehydration is investigated. This study provides valuable insights into how formulation parameters and excipients influence the architecture of LNPs after spray drying. The results will inform the rational design of LNP systems tailored for dry powder inhalation, advancing the development of effective inhaled RNA therapy.

Principal Investigator: Professor Jenny Lam
Experimenter: Dr Pratik Gurnani
Experimenter: Mr Leo Barr
Experimenter: Dr Fabrizia Foglia
Experimenter: Miss Elizabeth James Pathrapankal
Local Contact: Dr Najet Mahmoudi
Experimenter: Miss Ozde Oztekiner
Experimenter: Dr Chien-Ming Hsieh

DOI: 10.5286/ISIS.E.RB2610423

ISIS Experiment Number: RB2610423

Publisher: STFC ISIS Neutron and Muon Source

Data format: RAW/Nexus
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Data Citation

The recommended format for citing this dataset in a research publication is as:
[author], [date], [title], [publisher], [doi]

For Example:
Professor Jenny Lam et al; (2026): Using SANS to Probe Structural Changes of RNA Lipid Nanoparticles in Spray Dried Powder for Pulmonary Delivery , STFC ISIS Neutron and Muon Source, https://doi.org/10.5286/ISIS.E.RB2610423

Data is released under the CC-BY-4.0 license.