Analytical chemistryFeb 10, 2026

Detailed Size and Structure Analysis of mRNA-Carrying Lipid Nanoparticles Using Light and X-ray Scattering

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Feb 11, 2026

Abstract

The study demonstrates a novel method to analyze size distribution profiles of lipid nanoparticles used in drug delivery.

Assessment of lipid nanoparticles' safety, efficacy, and quality involves understanding both individual components and their organization.
A combination of methods including asymmetrical flow field-flow fractionation, synchrotron small-angle X-ray scattering, multiangle light scattering, and UV absorption provides insights into the nanoparticles' size and quality attributes.
Proposed model-free algorithms can analyze light scattering and X-ray scattering data to generate quantitative size distribution profiles.
Size-resolved information gathered includes drug loading, internal organization, and particle shape.
This approach allows for the evaluation of comparability between results from different systems and laboratories, supporting standardized quality control.

Simplified

The success of mRNA lipid nanoparticles (LNPs) used in the COVID-19 vaccines has demonstrated the significance of pharmaceutical products utilizing nanoparticle-based drug delivery systems in global healthcare. For the assessment of the safety, efficacy, and quality of these complex, multicomponent systems, it is important to consider not only the properties of the individual components but also their colloidal organization. There is a need for standardized methods to fulfill requirements for application in regular quality control, providing information on these properties in pharmaceutical products. To gain insight into size and size-resolved quality attributes of LNPs, we apply asymmetrical flow field-flow fractionation (AF4) coupled in-line with synchrotron small-angle X-ray scattering (SAXS) measurements, multiangle light scattering (MALS), and UV absorption measurements. We propose model-free algorithms for the analysis of light scattering and X-ray scattering data to obtain quantitative size distribution profiles from both methodologies. The approach is equally applicable for SAXS and MALS data, but SAXS additionally provides detailed, size-resolved insight into internal structure. Information on various quality-indicating parameters for the size-fractionated samples is obtained, including drug loading, internal organization, and particle shape. Since this approach does not require any model assumptions to obtain structural, quality-indicative information from experimental data, it is ideally suitable to evaluate the comparability of results from different systems and different laboratories. This makes it a valuable extension to the regular quality control panel for pharmaceutical nanoparticles, and it should be considered as a standard method in the pharmacopoeias.

Full Text

Full text is available at the source.

View Full Text ↗

Detailed Size and Structure Analysis of mRNA-Carrying Lipid Nanoparticles Using Light and X-ray Scattering

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the mrna technology brief