Hydration-induced lipid redistribution in swelling of controlled release liquid crystalline depots

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.