Thermoresponsive Sol-Gel System Incorporating Oleuropein-Rich Olive Leaf Extract for Enhanced Wound Healing and...

Oleuropein, the principal secoiridoid phenolic compound of olive leaves (Olea europaea L.), is recognized for its broad-spectrum antimicrobial, antibiofilm, antioxidant, and tissue-regenerative properties. However, its effective local therapeutic application remains challenging due to rapid clearance from the site of administration and limited residence time. In this study, an oleuropein-rich aqueous olive leaf extract was incorporated into a thermoresponsive sol-gel delivery system designed for localized application. The formulation was engineered to remain in a low-viscosity sol state at room temperature and to undergo a temperature-triggered sol-to-gel transition near physiological temperature (~33 °C), enabling in situ gel formation. Oleuropein content was quantified using a validated HPLC method, and the formulation was characterized with respect to physicochemical parameters, thermoreversible gelation behavior, particle size distribution, mechanical properties, and spreadability. Biological performance was evaluated through in vitro cytocompatibility (MTT assay), fibroblast migration (scratch assay), and collagen deposition (Sirius Red staining) in L929 fibroblasts, as well as antibiofilm activity against representative Gram-positive and Gram-negative bacterial strains. The developed sol-gel system demonstrated stable physicochemical characteristics, rapid and reversible thermogelation, suitable mechanical and spreading properties, concentration-dependent inhibition of biofilm formation, and acceptable cytocompatibility within the tested concentration range. Notably, the formulation supported fibroblast viability and collagen-associated responses at optimized concentrations. Overall, the results indicate that the proposed thermoresponsive sol-gel formulation represents a promising strategy for the localized delivery of oleuropein-rich olive leaf extract, combining physicochemical stability with dual wound-healing and antibiofilm functionality.