Molecular Exchange in Lipid Nanoparticles via Time-Resolved Small Angle Neutron Scattering

26 October 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The nano-scale dynamics of lipid nanoparticles (LNPs) for drug delivery play a large role in their function. Limited molecular motion is important for avoiding degradation prior to entering cells. Intracellularly, enhanced molecular motion is then vital for effective endosomal escape. We experimentally quantify such nano-scale dynamics through time-resolved small-angle neutron scattering (TR-SANS). This technique, previously leveraged only for simpler self-assembled systems, provides unprecedented insight to molecular behavior of LNPs. We find using TR-SANS in combination with traditional SANS and small-angle x-ray scattering (SAXS) that as pH drops below the pKa of the ionizable lipid, internal structure becomes more disordered and molecular exchange of cholesterol between LNPs occurs at a much faster rate. The results give insight into the behavior enabling delivery and provide a quantifiable metric by which to compare formulations. Successful analysis of this multi-component system also expands the opportunities for using TR-SANS to characterize other complex biomaterials.

Keywords

Neutron scattering
Lipid nanoparticles
Molecular exchange

Supplementary materials

Title
Description
Actions
Title
Supplementary Information
Description
Methods and supplementary figures
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.