Water Content in Nanoparticles Determined by Small-Angle Neutron Scattering and Light Scattering

The amount of water in therapeutic nanoparticles (NPs) is of great importance to the pharmaceutical industry, as water content reflects the volume occupied by the solid components. For example, certain biomolecules, such as mRNA, can undergo conformational change or degradation when exposed to water. Using static light scattering (SLS) and dynamic light scattering (DLS), we estimated the water content of NPs, including extruded liposomes of two different sizes and polystyrene (PS) Latex NPs. In addition, we used small-angle neutron scattering (SANS) to independently access the water content of the samples. The water content of NPs estimated by SLS/DLS was systematically higher than that from SANS. The discrepancy is most likely attributed to the larger radius determined by DLS, in contrast to the SANS-derived radius observed by SANS. However, because of low accessibility to the neutron facilities, we validate the combined SLS/DLS to be a reasonable alternative to SANS for determining the water (or solvent) content of NPs.