Ultrasound-assisted encapsulation of grape stem phenolic extracts into soft nanovesicles for enhanced dermocosmetic functionality

Ultrasound-assisted processes offer an efficient and sustainable approach for the preparation of vesicular systems containing plant-bioactive extracts. In this work, phenolic-rich extracts were recovered from grape stem by-products using subcritical water–ethanol pressurized liquid extraction and subsequently encapsulated into soft nanovesicles by ultrasound-assisted liposomization. Stems from Cabernet Sauvignon , Malbec and Tinto de la Pámpana Blanca were processed, with Malbec providing the highest polyphenol content (288 mg GAE/g extract) and antioxidant capacity (DPPH: 170 mg GAE/g extract; FRAP: 2.4 mMol FeSO₄/g extract). Ultrasonic cavitation-driven shear forces and microstreaming enabled the formation of different soft nanovesicular systems, including liposomes, ethosomes, propylene glycol vesicles (PEVs) and glycerol-containing PEVs (Gly/PEVs). All formulations displayed nanoscale sizes (162–229 nm), low polydispersity (PDI < 0.24), highly negative zeta potentials (−46 to −51 mV) and high encapsulation efficiencies (78–86%). Biocompatibility and protective efficacy were assessed in HaCaT keratinocytes. All nanovesicular systems showed good cytocompatibility (> 80% viability) and improved protection against H₂O₂-induced oxidative stress, with PEVs and Gly/PEVs maintaining cell viability close to control values (95–100%). Overall, these results indicate that ultrasound-assisted encapsulation of grape stem extracts into soft nanovesicles represents an effective approach to obtain stable bioactive-loaded nanosystems from winery by-products, with potential applications in dermocosmetic as bioactive delivery systems which are advanced carrier platforms designed to encapsulate, protect, and safely transport active compounds to target skin tissues.