Oxidation-Driven Assembly of Phenolic Compounds from Grape Seeds Waste into Nanoparticles as Potential Anti-Inflammatory and Wound Healing Therapies

Plant polyphenols have recently emerged as green nanoparticle (NP) precursors by oxidation-triggered assembly using oxidizing agents or in alkaline media. This study explored the potential of polyphenolic extracts derived from grape seed waste to serve as natural nanocarriers. Phenolic fractions were extracted from defatted grape seed waste, freeze-dried into powder, and characterized. Grape seed extracts (GSEs) of Obeidi and Asswad Karech, Lebanese autochthonous white and red grape varieties, respectively, had total phenolic contents (TPC) of 370 and 311 mg of gallic acid equivalents (GAE) per gram of dry matter, respectively, along with a high content of catechins, gallic acid, epicatechins, caffeic acid, syringic acid, and protocatechuic acid. GSE NPs were obtained by the oxidation-triggered self-assembly of Obeidi and Asswad Karech polyphenols in the presence of sodium metaperiodate as the oxidizing agent. The NPs exhibited a spherical morphology, hydrodynamic diameters of 109 and 142 nm, and zeta potential values of -20 and -19 mV for Obeidi and Asswad Karech, respectively. Both types of NPs showed high colloidal and chemical stability, even after storage for three months at 4 °C. They also demonstrated high antioxidant capacity, excellent biocompatibility in human dermal fibroblasts, and promising intracellular radical scavenging activity in stimulated RAW 264.7 macrophages. Furthermore, a gel formulation containing 2% Obeidi GSE NPs promoted wound healing with controlled infections and inflammation and faster tissue regeneration in a rat excision wound model. By day 19 of treatment, deep wounds treated with GSE NPs were fully healed with no visible scarring, while the untreated group showed deep scarring and discoloration. Our findings address the valorization of waste generated by wineries and present a promising natural nanocarrier with high stability, antioxidant properties, and anti-inflammatory activity.