Impact of non-ionizable lipids and phase mixing methods on structural properties of lipid nanoparticle formulations

Lipid nanoparticles (LNPs) were produced with sizes ranging from 50-225 nm and demonstrated notable differences in structural properties based on their formulation.

• The method of mixing (solvent-injection vs. microfluidic) significantly influenced nanoparticle size and order.
• Solvent-injection mixing produced larger (50-225 nm) and more ordered nanoparticles with approximately 5 nm inter-lamellar spacing.
• Microfluidic mixing resulted in smaller (50-75 nm) and more homogeneous nanoparticles.
• The stealth-lipid DSPE-PEG2000 had a significant impact on nanoparticle size, polydispersity, and encapsulation efficiency.
• Varying the type and content of phospholipids had only a marginal effect on the physicochemical properties of the LNPs.

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