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

Abstract

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.

Mesoscopic Structure of Lipid Nanoparticle Formulations for mRNA Drug Delivery: Comirnaty and Drug-Free Dispersions

“…Thus, it is assumed that the cholesterol is strongly enriched in the stabilizing shell but a rapid gradual reduction of the cholesterol concentration from the stabilizing shell toward the center of the core occurs. Nevertheless, a corresponding verification is beyond the interpretation limit of the available experimental data and is intended to be studied by upcoming contrast variation small angle neutron scattering (SANS, cf., e.g., ref ) measurements simultaneously with SAXS measurements at D22 (ILL, Grenoble). − It can, however, be concluded that the total volume of the lipids in the drug-free LNPs (EF samples) could quantitatively be determined within an experimental error of less than ±2% by the proposed combined SAXS/PCS data evaluation approach (cf. Table ).…”

Simple Scattering: Lipid nanoparticle structural data repository

“…SANS can take advantage of the natural neutron contrast between lipids and nucleic acids to probe different structural regions within LNPs. As an alternative approach, SANS can exploit the difference in scattering length density (SLD) between hydrogen ( 1 H) and deuterium ( 2 H or D) by isotopic labeling of LNP components to selectively highlight structural regions within LNPs, thus providing detailed insights into LNP morphology (Di Cola et al, 2016;Sebastiani et al, 2021;Leite et al, 2022;Urimi et al, 2022;Yang et al, 2022;Kangarlou et al, 2023). SANS can also provide quantitative information regarding the distribution of molecules within the LNP structure, including water content in solvated regions.…”