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