Dynamic Light Scattering Analysis of Lipid Nanoparticles: Effect of Salts on the Diffusion Interaction Parameter and Hydrodynamic Radius at Infinite Dilution

The rise in the popularity of lipid nanoparticle (LNP)-based formulations necessitates the need for screening tools to quickly predict their colloidal stability in the presence of common excipients. Protein chemists have employed the diffusion interaction parameter (k_D) determined using dynamic light scattering as an indicator of formulation stability, yet this approach has not been applied to particulate systems. Herein, k_D measurements of LNPs revealed behavior dissimilar to that of proteins. LNP interactions were inherently weakly attractive and unaffected by increasing concentrations of NaCl. The small change in the value in the presence of different salts was dependent upon salt molecular identity and consistent with the Hofmeister series. In addition, calculation of the hydrodynamic radius at infinite dilution (R_H,0) revealed a slight reduction in the LNP size with increasing NaCl concentration. Overall, while traditional k_D measurements provide limited information about LNP stability, the assay provides insight into physical changes to LNP in the presence of excipients via extrapolation of the diffusion coefficient to infinite dilution.