NMR-Based Molecular-Level Characterization: A Review of Its Application in Unveiling Lipid Nanoparticle Formulations

NMR spectroscopy offers vital atomic-level insights into lipid nanoparticles (LNPs), which are crucial for delivering nucleic acid therapeutics.

• NMR techniques provide detailed information on the chemical composition and molecular structure of LNPs.
• The method reveals how components like cholesterol and helper lipids affect the mobility and arrangement of ionizable lipids.
• Encapsulation of nucleic acids, such as small interfering RNA (siRNA), impacts LNP structure by interacting with and reducing the mobility of LNP components.
• NMR helps map the distribution of lipids and cargo within LNPs, enhancing understanding of their organization.
• The approach assesses how different preparation methods influence LNP heterogeneity and kinetic processes, such as the shedding of polyethylene glycol-conjugated lipids.

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