SAXS has proven particularly useful in several pharmaceutical applications. This section will describe the most important
Functionalization of self-assembled structures.
Self-assembled structures have provoked considerable interest because they can lead to functional materials with nanoscale
structures (11–13). SAXS can determine key relationships between nanostructures and their functions.
Scientists often use micelles, self-assemblies of amphiphilic molecules, to solubilize water-insoluble functional substances. Lyotropic liquid crystals
in lamellar and reversed-hexagonal phases are used for emulsion-type products. Liposomes or vesicles consisting of phospholipids
or synthetic surfactant bilayers play an essential role and act as nanocapsules. Polymer gels are used in various products,
including drug carriers.
Drug-delivery systems transport drugs to affected parts of the body. Nanocarriers, typically in the size range of 20 to 100
nm, provide the required amount of drugs promptly to a specifically affected part with pinpoint accuracy. Various self-assembly
systems (e.g., micelles, microemulsions, liposomes, cubosomes, and polymer-gel nanoparticles) have been tested as drug carriers.
Lytropics are important for biological systems. The SAXS method provides structural information about heterogeneities, aggregate
ordering, size, shape, separation, and intermolecular spacing within the aggregate stack and helps scientists study the interdependence
of morphology and phase behavior. The applications of liquid crystals include biological membranes (e.g., drug-delivery carriers).
Mesoporous materials have pore apertures similar in size to small biological molecules. Mesoporous materials with a narrow
pore-size distribution may thus be useful as hosts, supports, catalysts, and separation media for these molecules. The pore-size
distribution can be determined with SAXS.
The functionality of biological membranes depends on the geometrical and chemical properties of the amphiphilic molecules
of the membrane walls. Membrane parameters such as the electron-density profile or flexibility affect the membrane's functionality.
Permeability and the tendency to reorganize into micelles, lamellar stacks, or vesicles strongly depend on the internal arrangement
of the molecules in the bilayers.
The phospholipid-bilayer membranes can be studied with the SAXS for electron density, thickness, repeat distance of lamellae
and stacks, number of layers, packing, and flexibility parameters.
Proteins in solution.
Proteins are complex macromolecules. Many diseases are linked to protein misfolding. Structure changes may happen as a function
of time, pH, ionic strength, and changes in various solution conditions. SAXS helps identify structural states and changes
of biological macromolecules and helps correlate these changes to their biological functions. Over the past decades, 3-D structures
of a vast number of biological molecules have been determined using X-ray crystallography and nuclear-magnetic resonance (NMR)
(14). However, these high-resolution methods have their own limitations.
Structure determination by X-ray crystallography requires high-quality protein crystals that are complex and costly to produce.
NMR allows structures in solution to be studied, but the size of the protein typically accessible by NMR is still much smaller
than that of X-ray crystallography.
Some SAXS instruments allow simultaneous measurements of small and wide-angle X-ray scattering from proteins in solution.
SAXS successfully determines the ternary and quaternary structures by investigating the overall size and shape. The technique
has achieved considerable success in restoring 3-D structures of proteins from the scattering patterns. Experimental setups
with wide simultaneous and continuous q-ranges directly probe distance correlations on length scales that are small compared with the overall protein dimensions.
The setups may contain rich information about fine-structure details of proteins in solution (15–18). Scattering data in the
higher q region is sensitive to protein conformation states (i.e., secondary structures and their packing) and also enables scattering
patterns to be compared quantitatively with calculated patterns from detailed structure models. It can be used as an additional
information input for the evaluation of NMR data as well (19, 20).
To understand and predict protein crystallization from solutions have been paramount tasks for years. The SAXS method's sensitivity
helps it detect aggregate structures at an early stage and therefore allows it to indicate the optimum conditions for the
onset of protein crystallization.
Several diseases are associated with changes in the concentration of blood lipoproteins. SAXS performs fast and precise measurements
of lipoprotein particles using small amounts of sample. Its ability to measure all fractions of lipoproteins simultaneously
makes SAXS a cost-effective and convenient method for lipoprotein analysis in scientific studies and medical practices.
The SAXS method is useful in investigating native starch, its structure, and changes in the structure. The technique also
helps measure lamellar repeat distance, fractional lamellar crystallinity, width of the distribution of lamellar sizes, and
the number of semicrystalline repeats within each growth ring.
Small-angle X-ray scattering (SAXS) has emerged as an essential tool for structural analysis at length scales as large as
100 nm. The SAXS method yields information not only on particle size and shape, but also on the internal structure and radial
electron density profiles of disordered and partially ordered systems.
In the past, the experimental data only enabled the direct determination of overall particle parameters (e.g., mean radius
of gyration, particle symmetry, surface per volume) of the macromolecules. In terms of 3D models, the analysis was limited
to simple geometrical bodies (e.g., spherical, cylindrical, lamellar) or combinations of them.
The 1990s brought a breakthrough in SAXS data analysis methods that allowed ab initio shape and domain-structure determination and detailed modeling of macromolecular complexes using rigid body refinement (21–23).
In dense systems, the scattered intensity is a combination of single-particle scattering (i.e., form factor) and interparticle
scattering (i.e., structure factor). The generalized indirect Fourier transform method, one of the most recent developments
in data-evaluation programs, allows the interpretation of such scattering data (24). Information about interparticle interactions
in dense systems can be deduced by analyzing the structure factor with various potential models assuming repulsive or attractive
interactions. SAXS has become a powerful tool for pharmaceutical and biotechnology applications.
The author would like to thank Heimo Schnablegger, product manager of X-ray structure analysis at Anton Paar, for his comments
Gerd Langenbucher is a product manager for Physica rheometers and Anton Paar SAXSess X-ray structure analysis at Anton Paar USA, 10215 Timber
Ridge Dr., Ashland, VA 23005, tel. 804.550.1051, ext. 126, fax 804.550.1057, firstname.lastname@example.org