Small-Angle X-ray Scattering Unveils the Internal Structure of Lipid Nanoparticles

TL;DR

This study uses small-angle X-ray scattering to reveal the internal structure of lipid nanoparticles, providing insights into their composition, shape, and surfactant distribution, which are crucial for their application in nanomedicine.

Contribution

The paper presents detailed structural characterization of lipid nanoparticles using synchrotron SAXS, challenging classical models and informing better design for drug delivery.

Findings

Lipid nanoparticles have a barrel-like shape with coplanar lipid platelets.

Surfactant molecules form sticky patches between platelets, deviating from core-shell models.

Partial coverage of water interfaces affects drug loading and stability.

Abstract

Lipid nanoparticles own a remarkable potential in nanomedicine, only partially disclosed. While the clinical use of liposomes and cationic lipid-nucleic acid complexes is well-established, liquid lipid nanoparticles (nanoemulsions), solid lipid nanoparticles, and nanostructured lipid carriers have even greater potential. However, they face obstacles in being used in clinics due to a lack of understanding about the molecular mechanisms controlling their drug loading and release, interactions with the biological environment (such as the protein corona), and shelf-life stability. To create effective drug delivery carriers and successfully translate bench research to clinical settings, it is crucial to have a thorough understanding of the internal structure of lipid nanoparticles. Through synchrotron small-angle X-ray scattering experiments, we determined the spatial distribution and internal structure of the nanoparticles' lipid, surfactant, and the water in them. The nanoparticles themselves have a barrel-like shape that consists of coplanar lipid platelets (specifically cetyl palmitate) that are partially covered by polysorbate 80 surfactant and retain a small amount of hydration water. Although the platelet structure was expected, the presence of surfactant molecules forming sticky patches between adjacent platelets challenges the classical core-shell model used to describe solid lipid nanoparticles. Additionally, the surfactant partially covers the water-nanoparticle interface, allowing certain lipid regions to come into direct contact with surrounding water. These structural features play a significant role in drug loading and release, biological fluid interaction, and nanoparticle stability, making these findings valuable for the rational design of lipid-based nanoparticles.