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Phase behavior of soybean phosphatidylcholine and glycerol dioleate in hydrated and dehydrated states studied by small-angle X-ray scattering
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Camurus AB, Ideon Science Park, Gamma Building, Sölvegatan 41, SE-22379 Lund, Sweden.ORCID iD: 0009-0004-1983-0706
Camurus AB, Ideon Science Park, Gamma Building, Sölvegatan 41, SE-22379 Lund, Sweden.
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0002-9852-5440
2023 (English)In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 19, no 43, p. 8305-8317Article in journal (Refereed) Published
Abstract [en]

Soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) form liquid crystal nanostructures in aqueous environments, and their mixtures can effectively encapsulate active pharmaceutical ingredients (API). When used in a subcutaneous environment, the liquid crystalline matrix gradually hydrates and degrades in the tissue whilst slowly releasing the API. Hydration dependent SPC/GDO phase behavior is complex, non-trivial, and still not fully understood. A deeper understanding of this system is important for controlling its function in drug delivery applications. The phase behavior of the mixture of SPC/GDO/water was studied as a function of hydration and lipid ratio. Small-angle X-ray scattering (SAXS) was used to identify space groups in liquid crystalline phases and to get detailed structural information on the isotropic reverse micellar phase. The reported pseudo ternary phase diagram includes eight different phases and numerous multiphase regions in a thermodynamically consistent way. For mixtures with SPC as the predominant component, the system presents a reverse hexagonal, lamellar and R3m phase. For mixtures with lower SPC concentrations, reverse cubic (Fd3m and Pm3n) as well as intermediate and isotropic micellar phases were identified. By modeling the SAXS data using a core–shell approach, the properties of the isotropic micellar phase were studied in detail as a function of concentration. Moreover, SAXS analysis of other phases revealed new structural features in relation to lipid–water interactions. The new improved ternary phase diagram offers valuable insight into the complex phase behavior of the SPC/GDO system. The detailed structural information is important for understanding what APIs can be incorporated in the liquid crystal structure.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2023. Vol. 19, no 43, p. 8305-8317
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:mau:diva-63665DOI: 10.1039/d3sm01067hISI: 001096679900001PubMedID: 37819242Scopus ID: 2-s2.0-85175015955OAI: oai:DiVA.org:mau-63665DiVA, id: diva2:1811529
Available from: 2023-11-13 Created: 2023-11-13 Last updated: 2025-11-18Bibliographically approved
In thesis
1. Structure, Phase Behaviour, And Swelling Kinetics Of Lipid-Based Drug Delivery Depots
Open this publication in new window or tab >>Structure, Phase Behaviour, And Swelling Kinetics Of Lipid-Based Drug Delivery Depots
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis examines the structural and kinetic properties of lipid-based drug delivery depots, with a particular focus on Camurus' FluidCrystal® injection technology. The aim is to enhance and the understanding of lipid depot formation, thereby contributing to the development of the drug delivery platform.

We investigated the phase behaviour of soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) mixtures, both in dry and hydrated states, using small-angle X-ray scattering (SAXS), revealing how lipid composition and water content influence the phase behaviour. Succeeding research explored the thermotropic behaviour of SPC, egg phosphatidylcholine (EPC), and dioleoylphosphatidylcholine (DOPC), highlighting the impact of lipid properties on structural transitions.

To understand lipid depot behaviour in aqueous environments, we studied the swelling kinetics using Karl Fischer titration and magnetic resonance imaging (MRI), which revealed the inhomogeneity at equilibrium. These findings were explored further by examining the hydration-induced lipid redistribution within lipid depots, employing techniques such as SAXS at synchrotron facilities and Raman spectroscopy. Lastly, the compatibility of FluidCrystal® formulations with hemp extract was assessed, demonstrating the system's robustness in incorporating active compounds.

These findings improve the understanding of lipid-based systems and support future research on formulations with active compounds and varied lipid compositions.

Place, publisher, year, edition, pages
Malmö: Malmö University Press, 2025. p. 70
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383, E-ISSN 2004-9277 ; 2025:11
National Category
Physical Chemistry
Identifiers
urn:nbn:se:mau:diva-79176 (URN)10.24834/isbn.9789178776580 (DOI)978-91-7877-657-3 (ISBN)978-91-7877-658-0 (ISBN)
Public defence
2025-09-26, AS:E002/HS auditorium, Jan Waldenströms gata 25, Malmö, 09:00 (English)
Opponent
Supervisors
Note

Paper IV and paper V in dissertation as manuscript. 

Paper V not included in the fulltext online. 

Available from: 2025-09-02 Created: 2025-09-01 Last updated: 2025-11-18Bibliographically approved

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Engstedt, JenniBarauskas, JustasKocherbitov, Vitaly

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