SHS Web of Conferences, open access proceedings in Humanities and Social Sciences

Background/Objectives: Oleuropein is a bioactive phenolic compound from olive leaves with antimicrobial and antioxidant activity. This study aimed to develop a sprayable oral gel containing an oleuropein-rich aqueous extract and to evaluate its pharmaceutical performance antimicrobial efficacy and in ovo biological response. Methods: Oleuropein content was quantified using a validated chromatographic method. Polymeric systems were screened to select an optimized sprayable formulation. Physicochemical stability, dose uniformity, and antimicrobial activity against major cariogenic bacteria were evaluated. In ovo biological evaluation was conducted using the chick chorioallantoic membrane angiogenesis model together with histopathological examination of embryonic heart and liver tissues. Results: Oleuropein content was determined as 288.6 µg/mL in the olive leaf extract and 255.1 µg/mL in the final formulation. The optimized oral spray showed stable physicochemical properties, with pH maintained at 6.90 ± 0.02 and no relevant changes in viscosity during storage. The mean delivered dose per actuation was 0.128 ± 0.015 g, corresponding to 32.6 µg oleuropein per spray. The formulation exhibited inhibitory activity against all tested cariogenic microorganisms, with MIC values ranging from 13.3 to 170.7 µg/mL and MBC values generally two-fold higher. In the CAM assay, significant concentration- and time-dependent antiangiogenic effects were observed after 24–48 h at moderate and higher concentrations. Histopathological evaluation revealed dose-dependent acute degenerative and congestive changes in heart and liver tissues without evidence of fibrosis or steatosis. Conclusions: The oleuropein-based sprayable oral gel is a promising localized delivery system with adequate stability dose uniformity and antimicrobial efficacy. In ovo findings provide a conservative assessment of systemic exposure and support further development for oral biofilm and caries-related applications.

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.