Valorization of Olive Leaf Extract via Tailored Liposomal Carriers: Comparative Analysis of Physicochemical Features, Antioxidant Capacity, and Stability

<b>Background/Objectives</b>: Olive leaf (<i>Olea europaea</i> L.), a by-product of olive oil production, is rich in bioactive phenolics but limited in application due to poor solubility and stability. To improve their bioavailability, this study presents a comparative encapsulation strategy using three phospholipid-based liposomal systems (AL, PG90, and PH90) loaded with ethanolic olive leaf extract. <b>Methods</b>: Liposomes were characterized by physicochemical parameters, encapsulation efficiency (EE), antioxidant activity, morphology, release kinetics under simulated physiological conditions, and 60-day stability. To the best of our knowledge, this is the first direct comparison of AL, PG90, and PH90 matrices for olive leaf extract encapsulation. <b>Results</b>: HPLC and GC-MS confirmed successful encapsulation, with oleuropein showing the highest EE (up to 76.18%). PH90 favored retention of non-polar triterpenes, while AL and PG90 preferentially encapsulated polar flavonoid glycosides. FT-IR analysis verified extract integration into phospholipid bilayers. Antioxidant activity remained high in all loaded formulations, with negligible activity in empty liposomes. Extract-loaded systems exhibited reduced particle size, higher viscosity, and more negative electrophoretic mobility, enhancing colloidal stability. PG90 liposomes displayed the most stable mobility profile over 60 days. Transmission electron microscopy and nanoparticle tracking analysis revealed formulation-dependent vesicle morphology and concentration profiles. Release studies demonstrated significantly prolonged polyphenol diffusion from PG90 liposomes compared to the free extract. <b>Conclusions</b>: Phospholipid composition critically governs encapsulation selectivity, stability, and release behavior. Tailored liposomal systems offer a promising strategy to enhance the stability and delivery of olive leaf polyphenols, supporting their application in bioactive delivery platforms.