SAXS and SANS case studies
1. Resolving the Internal Structure of Particles in Solution
Objectives
- Extract quantitative structural information from synchrotron-SAXS data collected on particles in solution, at low and high concentration, using direct model fitting
- Distinguish the intrinsic morphology from interparticle interactions to obtain structural parameters.
ResultsThe detailed morphology of polymeric micelle, i.e. size, shape, internal structure and size distribution, could be determined via our form-factor and structure-factor modelling approach, with the aid of Pair-distance distribution function P(r). Buffer- and concentration-dependent structural changes could be accurately quantified thanks the quality of the SAXS signal collected at a synchrotron beamline.
Applications
- Characterization of a broad range of particles in solution: micellar systems formed by surfactants, lipids, and amphiphilic polymers in pharmaceutical formulations
- Development of DS formulation, screening of novel excipients, drug loading studies, stability studies, and batch-to-batch comparability.
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2. Next-Generation Structural Characterization Tool to Optimize Micelle-Based Drug Delivery Systems
Objectives
- Design and select surfactant candidates for effective micelle-based drug delivery systems, capable of solubilizing poorly soluble APIs and protecting them from detrimental in vivo conditions, e.g. pH and Ca2+ ions in the gastrointestinal tract
- For this purpose, develop a novel structural characterization tool based on Pair Distribution Function (PDF) moments derived from SAXS measurements
Results
- Our new model based on PDF moments was able to characterize successfully the micelle morphology and its interactions with the poorly soluble API and Ca2+ ions, providing detailed insights into their size, shape, and electron density contrasts.
- We were able to estimate the relative fractions of the API in the core and shell of the micelle
- The model also revealed how the presence of Ca2+ ions reduces the incorporation of API both within the hydrophobic core and across the micelle system.
Applications
This advanced yet straightforward analytical model represents a powerful tool for formulation scientists, to characterize and optimize robust, high-performance drug delivery systems that can enhance the bioavailability of poorly soluble APIs and protect them against detrimental in vivo conditions.
De Caro et al. (2023), Small Angle X-Ray Scattering Data Analysis and Theoretical Modelling for the Size and Shape Characterization of Drug Delivery Systems Based on Vitamin E TPGS Micelles, J. Pharm. Sci, 112, 243.
https://doi.org/10.1016/j.xphs.2022.09.029
De Caro et al. (2024), Characterization of Surfactant Spheroidal Micelle Structure for Pharmaceutical Applications: A Novel Analytical Framework, Pharmaceutics, 16(5), 604.
https://doi.org/10.3390/pharmaceutics16050604
De Caro et al. (2025), Characterization of VitE-TPGS Micelles Linked to Poorly Soluble Pharmaceutical Compounds Exploiting Pair Distribution Function's Moments, Pharmaceutics, 17(4), 431.
https://doi.org/10.3390/pharmaceutics17040431
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3. Characterizing the Coexistence of Monomeric Macromolecule with their Assemblies
Objectives
Investigate the structure of macromolecular systems that may have self-assemblies coexisting with single molecules in solution
Results
A hybrid scattering model has been developed that could accurately reproduce the experimental synchrotron-SAXS signal, capturing the coexistence of self-assembled and monomeric macromolecules. The model can reveal the morphology (quantitative size parameters) of both entities (sphere, ellipsoid, rod, circular cylinder, elliptic cylinder)
Applications
- Characterization of macromolecule DS in solution, such as DNA and RNA oligonucleotides (single- and double-stranded, chemically modified) at various concentrations
- Development of DS formulation and screening of novel excipients to prevent aggregation at high doses
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4. Quantifying Drug Loading in Surfactant Micelles as Drug Delivery System
ObjectivesCharacterize and quantify drug loading in surfactant micelles as drug delivery system
ResultsFitting of the synchrotron-SAXS signal enabled the estimate of the number of drug molecules per micelle and the characterization of induced structural changes (micelle core size, shell thickness, electron density and overall morphology).
Applications
- Characterization of small-molecule and peptide DS incorporation into micelles and other drug delivery systems
- Design and screening of novel surfactants for micellar drug delivery systems
- Optimization of DS-surfactant molecular ratio
- In-vitro studies on the protective role of micellar drug delivery systems to simulate physiological conditions (effect of pH, Ca2+, etc)
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5. Probing the Structural Organization of Pluronic L62–Aerosol-OT Co-Micelles via SANS
Objectives
- Investigate the thermal stability of co-micelles formed by surfactant–polymer mixtures, and elucidate their drug intake and release mechanisms
- Correlate structural evolution with composition and temperature under formulation-relevant conditions
ResultsStructural changes in size and geometry as a function of the relative composition of L62 and AOT could be quantitatively determined via from the SANS signal, together with temperature-dependent stability. The number of AOT molecules per micelle is tunable via concentration and temperature, enabling controlled uptake and release of charged drugs governed by charge neutrality.
Applications
- Structural characterization of co-micellar and polymer–surfactant systems in advanced charged-drug delivery formulations, including high-concentration systems
- Mechanistic studies of intermolecular interactions, thermal stability, and charge-regulated loading, supporting the rational design of tunable drug carriers.
Zhou, B., et al. (2020), Complexation of Pluronic L62 (EO6)–(PO34)–(EO6)/aerosol-OT (sodium bis(2-ethylhexyl)sulfosuccinate) in aqueous solutions investigated by small angle neutron scattering, Phys. Chem. Chem. Phys., 22, 12524-12531.
https://doi.org/10.1039/D0CP00603C
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6. Identifying the crystalline structure of lipidic liquid crystals for controlled drug release
Objectives
Characterize the crystalline structure (Bragg peak positions, phase identification and structural parameters) of lipidic liquid crystals, formed from the self-assembly of amphiphilic lipids at high concentration
Results
From the synchrotron-SAXS signal, characteristic peak ratios could be indexed to assign the corresponding crystalline or liquid-crystalline phases, and in some cases, two distinct phases were identified based on peak indexing. Lattice parameters and domain information were quantitatively extracted from the fitted peak positions.
Applications
- Structural characterization of bicontinuous cubic and other ordered crystalline phases formed by amphiphilic molecules.
- Determination of heterogeneity and spatial mapping
- Rational design and optimization of lipid liquid crystal platforms for controlled drug release
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7. Revealing the Peripheral Counterion Cloud of Soft Microgels via SANS
Objectives
- Amplify the weak scattering signal of polymer microgel counterion clouds for direct structural measurement
- Isolate and resolve the counterion distribution that is otherwise obscured by the dominant particle scattering.
ResultsUsing SANS contrast variation, the weak counterion signal could be selectively enhanced, enabling direct determination of counterion cloud geometry. The analysis revealed the localization at the particle periphery, providing quantitative evidence for counterion-induced osmotic compression consistent with spontaneous deswelling.
Applications
Direct measurement of the counterion cloud, enabled by the unique contrast variation capability of SANS (not possible with SAXS):
- Supports the rational design of soft drug carriers by revealing how charges and ions are distributed around particles—factors that strongly influence drug loading and release
- Provides insights into the behavior of concentrated soft-particle formulations by clarifying how ionic interactions affect interparticle forces, compressibility, viscosity, and injectability.
Zhou, B., et al. (2023), Measuring the counterion cloud of soft microgels using SANS with contrast variation, Nat. Commun. 14, 3827.
https://doi.org/10.1038/s41467-023-39378-5
Zhou, B. and Gasser, U. (2023), Poly(N-isopropylacrylamide) microgel swelling behavior and suspension structure studied with small-angle neutron scattering, Phys. Rev. E, 108(5), 054604.
https://doi.org/10.1103/PhysRevE.108.054604
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