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.

Lipid-based drug delivery systems offer the potential to enhance bioavailability, reduce dosing frequency, and improve patient adherence. In aqueous environment, initially dry lipid depots take up water and form liquid crystalline phases. Variation of lipid composition, depot size and hydration-induced phase transitions will plausibly affect the diffusion in and out of the depot. Lipid depots of soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) mixtures were hydrated for varying time durations in a phosphate-buffered saline (PBS) buffer and then analyzed with Karl Fischer titration, magnetic resonance imaging (MRI) and gravimetrically. Mathematical modeling of the swelling process using diffusion equations, was used to estimate the parameters of diffusion. Both composition of lipid mixture and depot size affect swelling kinetics… The diffusion parameters obtained in Karl Fischer titration and MRI (with temporal and spatial resolution respectively) are in good agreement. Remarkably, the MRI results show a gradient of water content within the depot even after the end of diffusion process. Apparently contradicting the first Fick's law in its classical form, these results find an explanation using the generalized Fick's law that considers the gradient of chemical potential rather than concentration as the driving force of diffusion.

The main objective of the present study was to investigate mixtures of soy phosphatidylcholine (SPC) and glycerol dioleate (GDO) as encapsulation matrices for Cannabis sativa L. phytocannabinoids. The effects of cannabinoids loading into non-aqueous formulations and non-lamellar liquid crystalline phases were studied using synchrotron small-angle X-ray diffraction and dynamic light scattering methods. The incorporation of phytocannabinoids is discussed with respect to the lipid aggregation behaviour, self-assembled nanostructures, and long-term chemical stability. The obtained results showed that SPC/GDO-based formulations can incorporate relatively high amounts of cannabinoids and could serve as liquid crystalline delivery vehicles in the form of bulk phases.

Lipid liquid crystalline (LLC) depots are a useful platform for controlled drug release due to their biocompatible characteristics and slow-release kinetics. Despite research into their bulk phase behavior, spatially resolved insights into the structural transitions within heterogeneous regions remain limited. In this study, advanced synchrotron SAXS capabilities are employed to investigate hydration-induced phase transitions with high spatial resolution, complemented by Raman scattering to study lipid distribution. The results reveal that hydration drives lipid distribution within the depot and causes the formation of a hexagonal outer layer and a cubic micellar inner structure. Lipid redistribution is revealed as a significant factor slowing down swelling kinetics and associated properties of the drug delivery vehicle, leading to concentration and structure gradients persisting on the time scale of weeks. These findings are expected to support the rational design and optimization of lipid-based drug delivery systems.