Idiosyncratic behaviour of pegylated lipid nanoparticles used in RNA delivery: A dynamic light scattering study

Dynamic light scattering (DLS) is commonly employed to estimate the hydrodynamic radius of particles (R_H) and less commonly to assess colloidal stability. Here we suggest DLS can also be used to study the interface between the particle and the surrounding water. DLS R_H measurement have two sources of systematic error. Attraction and repulsion between particles alter the apparent R_H in concentration dependent manner referred to as the interaction parameter (k_D). The second systematic error, which is not concentration dependent, is observed as a change in the calculated hydrodynamic radius at infinite dilution (R_H,0). If the actual R_H,0 is unchanged, the variation can be attributed to a change in apparent viscosity (η_app) and that η_app is the viscosity at the slipping plane. Pegylated lipid nanoparticles (LNPs) were measured at various temperatures using DLS. The calculated R_H,0 of the LNPs decreased markedly with rising temperature. The authors suggest that the radius is unlikely to change, but the η_app decreased with an increase in temperature. Salts from the Hofmeister series caused a minimal change in the R_H,0, η_app or k_D values. This suggests that charge screening is not a key determinant of LNP colloidal stability. The addition of isopropanol increased the η_app values. This suggests that both isopropanol and temperature affect the apparent viscosity at the slipping plane between the pegylated LNP and water.