Enhanced Characterization of LNP with Multi-Angle Dynamic Light Scattering (MADLS)

The use of lipid nanoparticles (LNP) technology continues as applications supported by reproducible and scalable manufacturing surge. However, obtaining regulatory approval for products utilizing LNP can be a significant hurdle.

Meeting the requirements of global regulatory agencies can be challenging for LNP developers, as it often requires extensive study and documentation of product functions and manufacturing processes. This can greatly consume time and resources for developers who need to balance thorough validation necessary to ensure product safety, stability, and efficacy with the need to bring products to the market as quickly as possible.

Thus, developers need methods to efficiently and effectively characterize LNP delivery vectors.

What role does MADLS play?
Accurately determining the biophysical characteristics of a product is crucial for successful development and approval.

Dynamic light scattering (DLS) is an accepted method for the analysis of the biophysical characteristics of LNP. It is a powerful tool for determining particle size and agglomeration. Traditional DLS illuminates particles’ light scattering at a specified single angle using a light source. It then analyzes the fluctuations in scattering intensity to calculate particle size.

Multi-angle dynamic light scattering (MADLS) has taken it a step further. By measuring a sample at various angles, MADLS provides enhanced resolution and accuracy compared to traditional DLS, offering a more precise representation of various-sized particles in the sample, allowing developers to have greater confidence in their results.

Learn more about MADLS

DLS and MADLS: Slightly different answers to the same question
Both DLS and MADLS are routinely used to assess batch-to-batch consistency and can cover a wide range of particle sizes, but MADLS is particularly useful for LNP developers who need more detailed information on populations within a sample. This is because, in addition to providing a high-resolution particle size distribution (PSD) that precisely represents various-sized particles in the sample, MADLS also provides particle concentration for each distinct population, aiding developers in unlocking insights that facilitate further developments, including effective LNP-based mRNA delivery.

Size distribution obtained with single-angle DLS (red) and MADLS (green). It shows higher resolution and displays actual two particle populations.

Read the application note for a more detailed and direct comparison of DLS and MADLS capabilities. Read the application note. What can MADLS tell us about LNP samples and when should it be used?

Benefits of using MADLS during LNP development and manufacturing stages
· Representative measurement of particle size with reduced flattening
· Angle-independent PSD
· Enhanced resolution for multicomponent nanoparticle dispersion characterization
· Size-resolved concentration measurement of particles that are irreducible by orthogonal techniques

How can MADLS support product development?
· Evaluate batch consistency over time
· Provide insight into potential instability of samples
· Detect small populations of larger aggregates in the sample
· Serve as an orthogonal verification to other particle concentration measurement techniques such as nanoparticle tracking analysis (NTA) or enzyme-linked immunosorbent assay (ELISA).

A powerful combination for mRNA-LNP analysis
In recent studies, our researchers analyzed two mRNA-LNP formulations using both DLS and MADLS with the Zetasizer Ultra. The analysis was automatically optimized by integrated software (ZS XPLORER), with five replicates conducted.

This enlightening experiment demonstrated the practical capabilities and cross-verification provided by complementing DLS with MADLS, as well as the versatility of the Zetasizer Ultra. The resulting compositions for the two samples revealed that DLS and MADLS each provide unique insights into particles.

Read the application note What can MADLS tell us about LNP samples and when should it be utilized? to access full details on methods and results and learn how MADLS can aid in LNP development.