Small angle X-ray Scattering (SAXS) is a unique technique for studying liposomes.
It combines the following key characteristics: X-ray technique: SAXS is able to penetrate the outer surface and offers insights into the important internal structure of liposomes. Non-intrusive: SAXS does not require special sample (pre)-processing or treatment such as filtering, heating, freezing or drying, and provides a true view of the structure and interactions in a natural environment. High information content: Structural and interaction information. Apart from overall size, shape and internal structural parameters, biomolecular interactions, binding (e.g. proteins and ligands) and aggregation can also be studied.
Fast screening capability: Being a relatively fast and automated technique, SAXS can be used to monitor structural and stability changes under varying formulation conditions or temperature. |
|
Technique complementarity: SAXS provides unique as well as orthogonal information to other common techniques. This makes SAXS a truly synergetic technique in combination with other features in fast obtainable techniques. For example, electron microscopy (EM) data can assist in interpretation of SAXS data and SAXS can validate EM data in solution and be used to easily track identified features under varying conditions. | |
SAXS insights into liposome properties and formulationsSize and shape information
Functional properties and stability of formulations, interactions, encapsulation and release properties can all be impacted by the size and shape of a liposome.
|
|
Lamellarity The lamellarity can influence the encapsulation capacity and release kinetics of liposomes.
Membrane thickness
Internal structure
|
Interactions with other molecules
Structural changes under varying conditions:
|
Correlating interaction parameters and drug propertiesDrug encapsulation and release: SAXS can provide insights into the interaction between liposomes and encapsulated drugs. By comparing the scattering profiles of empty liposomes and drug-loaded liposomes, one can investigate the structural changes in liposomes upon drug encapsulation. Additionally, SAXS can be used to study the release kinetics of drugs from liposomes under different conditions, such as temperature or pH variations.
|
|
Protein-liposome interactions: SAXS can be used to study the binding and interactions of proteins with liposomes, providing information on the location and orientation of the protein within the lipid bilayer or at the liposome surface. This information can help understand how proteins interact with liposome-based drug delivery systems or how membrane proteins are embedded in lipid bilayers.
Liposome fusion and aggregation: SAXS can be used to study the fusion and aggregation of liposomes, which are important processes in various biological and pharmaceutical applications. By analyzing the scattering profiles of liposome mixtures under different conditions, one can gain insights into the mechanisms of liposome fusion and aggregation. |
Environmental factors: SAXS can be employed to investigate how environmental factors, such as pH, temperature, ionic strength, or the presence of other solutes, affect liposome structure and stability. This information can be crucial for optimizing liposome formulations and understanding their behavior in physiological environments.
Liposome-liposome interactions: SAXS can be used to study the interactions between different liposome populations, including the formation of multi-lamellar structures or the phase behavior of liposomes with varying lipid compositions. This information can help understand the behavior of liposome mixtures and the factors influencing their stability.
|
Correlating structural parameters and drug propertiesEncapsulation efficiency:The size of the internal aqueous core and the organization of the lipid bilayer can impact the encapsulation efficiency of hydrophilic drugs, while the bilayer structure and lipid composition can influence the encapsulation of hydrophobic drugs. |
Release kinetics: The bilayer thickness, lipid composition, and overall liposome size can affect the release kinetics of the encapsulated drug. A thicker bilayer or a more rigid liposome structure may result in slower drug release, while a more fluid or porous structure can lead to faster release.
Stability: The liposome’s internal structure, including lipid composition and bilayer organization, can influence its stability under various conditions, such as temperature, pH, and mechanical stress. A more stable liposome structure can protect the encapsulated drug from degradation and improve its shelf life. |
- Shear, pore size release: https://onlinelibrary.wiley.com/doi/full/10.1002/anbr.202200101
- Dissolution: https://www.sciencedirect.com/science/article/pii/S2590156722000020
- General SAXS/SANS Liposome study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985204/
- Review: https://www.mdpi.com/1999-4923/14/12/2704#B19-pharmaceutics-14-02704
- Lysophilisation: https://www.researchgate.net/figure/SAXS-patterns-of-liposomes-before-and-after-freezing-and-lyophilisation-As-a_fig5_46035000
- Protein/Peptide-liposome interactions: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209755/
- Liposome-liposome interactions: https://www.sciencedirect.com/science/article/pii/S0006349518303412
- Liposome characterization using SAXS & SANS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932473/