Revealing the temperature-pH phase transitions of lipid nanoparticles through high throughput SAXS

Lipid Nanoparticles (LNPs) have attracted considerable attention as promising drug carriers due to their biocompatibility and ability to encapsulate hydrophobic drugs and genetic cargo. Understanding the thermal behavior and phase transitions of LNPs is crucial for optimizing their stability and drug-loading capacity.

Small-Angle X-ray Scattering (SAXS) is a non-destructive technique that allows us to study the structural characteristics of LNPs in solution. Since SAXS probes length scales across several orders of magnitude, it can simultaneously deliver information about the overall size and internal lipid structure of a LNP. Furthermore, since SAXS can be performed in a high throughput manner, it can probe a large conformational space of formulations and conditions. These two properties make SAXS an excellent technique to measure the phase diagrams of lipid nanoparticles.

In this application note we used high throughput SAXS to measure the temperature-pH phase diagram of RNA loaded lipid nanoparticles using two different data treatment analyses:
– an empirical approach comparing SAXS data sets similarity, and
– a scattering physics-based analysis approach following evolution of scattering curve parameters.

Header image credit: [Dr_Microbe] –