Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the Structure of Drug-Loaded Liposomes

Abstract

Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and shape and (ii) cargo upload/release with unmodified properties. Structural issues are of primary importance to control the mechanism of action of loaded vectors. Overall properties, such as mean diameter and surface charge, can be obtained using bench instruments (Dynamic Light Scattering and Zeta potential). However, techniques with higher space and time resolution are needed for in-depth structural characterization. Small-angle X-ray (SAXS) and neutron (SANS) scattering techniques provide information at the nanoscale and have therefore been largely used to investigate nanovectors loaded with drugs or other biologically relevant molecules. Here we revise recent applications of these complementary scattering techniques in the field of drug delivery in pharmaceutics and medicine with a focus to liposomal carriers. In particular, we highlight those aspects that can be more commonly accessed by the interested users.

Biomolecule–polymer hybrid compartments: combining the best of both worlds

“…Similarly, the elastic scattering of neutrons (SANS) or X-rays (SAXS) at small angles can be used to get more detailed information about the morphology, shape and structure of polymeric membranes and compartments, but is limited by the need of appropriate radiation facilities. 38,39 Nanoparticle tracking analysis (NTA) combines visualization with scattering. The light scattered by single vesicles is tracked by a CCD camera and used to calculate the vesicle concentration and the hydrodynamic diameter by Stokes-Einstein relation.…”

A Novel Approach to Increase the Stability of Liposomal Containers via In Prep Coating by Poly[N‐(2‐Hydroxypropyl)Methacrylamide] with Covalently Attached Cholesterol Groups

“…To obtain detailed information about the internal structure of the stabilized liposomes, small‐angle X‐ray scattering (SAXS) experiments were performed (see details in Supporting Information). Due to different contrast for scattering length densities of hydrophobic and hydrophilic membrane layers, the SAXS data provide a closer look into the membrane structure; thus, this technique is widely used to study liposomes . Experimental data (Figure S8, Supporting Information) were fitted with SASfit software .…”

“…Due to different contrast for scattering length densities of hydrophobic and hydrophilic membrane layers, the SAXS data provide a closer look into the membrane structure; thus, this technique is widely used to study liposomes. [26,27] Experimental data ( Figure S8, Supporting Information) were fitted with SASfit software. [28] The "sphere with three shells" (Figure 4, Stage II) was chosen to fit the obtained experimental data, where a sphere with radius R represents the inner "hollow" water volume of the vesicle, t sh2 -the thicknesses of the hydrophobic layer formed by alkyl PC chains, t sh1 and t sh3the thickness of inner and outer hydrophilic layers, respectively.…”

Synchrotron Scattering Methods for Nanomaterials and Soft Matter Research

“…Small-angle neutron scattering (SANS) and SAXS methods have been widely used for the elucidation of the morphology and internal organization of liposomes and other lipid nanoparticles loaded with drugs [19,43]. A key advantage is that measurements can be carried out in the same conditions of the pharmaceutical formulations.…”