Valorization of native grape pomace through vesicular nanocarriers for the enhanced delivery of high-value natural bioactive compounds in green cosmeceutical applications

Agro-industrial by-products such as grape pomace represent a sustainable source of bioactive phenolic compounds; however, their practical application in cosmeceutical formulations is limited by their chemical instability, heterogeneous composition, and low skin bioavailability. Although vesicular nanocarriers have been widely proposed to overcome these limitations, their interaction with complex polyphenolic matrices remains poorly understood, and comparative studies across different vesicle types are still scarce. In this context, the present work tests the hypothesis that the composition and physicochemical properties of vesicular systems differentially modulate the encapsulation efficiency, stability, and biological activity of grape pomace-derived phenolics. Grape pomace extracts from three red grape varieties ( Cabernet Sauvignon, Malbec, Tinto de la Pámpana Blanca ) were obtained using a green extraction approach and characterized in terms of yield, total phenolic content and antioxidant capacity. The most promising extract, Tinto de la Pámpana Blanca , was incorporated into four vesicular systems (liposomes, ethosomes, transfersomes and Transcutol® P penetration enhancer containing vesicles (PEVs)) which were evaluated in terms of physicochemical properties, encapsulation efficiency and biological performance in keratinocytes under oxidative stress. Results demonstrate that vesicle composition significantly influences both colloidal stability and biological response. Ethosomes exhibited the highest encapsulation efficiency (>96%) and colloidal stability. However, PEVs demonstrated the most pronounced cytoprotective effect in keratinocytes, preserving up to 97% viability following oxidative damage. These findings highlight the potential of Tinto de la Pámpana Blanca pomace as a valuable upcycled cosmeceutical ingredient and underscore the role of the vesicular systems in stabilizing and enhancing antioxidant efficacy for topical applications. • Grape pomaces, by-products with great potential as source of phenolic compound. • Tinto de la Pamapana Blanca grape pomace extract, high dermo-functional value. • Vesicles improve the stability of the extract and enhance oxidative stress protection. • PEVs shined in protection due to the preservation of 98 % keratinocyte viability.