Tailoring Lipid-Based Drug Delivery Nanosystems by Synchrotron Small Angle X-ray Scattering

Thanks to specific physico-chemical properties, drug delivery systems based on nanoparticles have proven to effectively transport delicate molecules for therapeutic purposes, protecting them from degradation, increasing their stability in the blood circulation and allowing to convey and release the transported substances in specific areas of the body. Nanoparticles obtained from biopolymers for applications in medicine and pharmaceutics have become particularly popular in recent years due to the enormous research effort in the field of vaccines to respond to the pandemic emergency. Among the various types of biopolymers used to produce nanoparticles for therapeutics, lipids have characteristics that make them biocompatible, with low toxicity and ease of clearance. They can be synthesized by designing their characteristics according to the foreseen administration path, or to the target of the transported drug. The analytical methods mostly used to evaluate the characteristics of lipid nanosytems for drug delivery involve studying their effects on cells, in vitro and in vivo. Although it is often considered a "niche technique" for research in the bio-related sciences, Small Angle X-ray Scattering (SAXS) is a versatile tool to study the structure of nanosystems based on lipids, both ex situ and in situ. Therefore, it allows to evaluate both the effect of the different synthesis parameters and of the exposure of lipid nanoparticles to physiological conditions, which is of fundamental importance to design efficient drug delivery systems. In this mini-review, we will report some recent examples of characterization and design of nanoparticles based on lipids, where SAXS has been a fundamental step both to guide the synthesis of nanomaterials with tailored characteristics, and to understand the interaction between nanomaterials and cells.