Grape seeds are a rich source of bioactive compounds, especially polyphenols, which are known for their antioxidant and anti-aging properties. The aim of this study was to extract phytochemicals from the Lebanese grape variety “Obeidi” and incorporate them into liposomes and hyalurosomes in order to select the most effective formulation for improving skin properties and protecting against oxidative damage. Grape seeds were extracted by a sustainable ethanol-water method, yielding a total phenolic content (TPC) of 376 ± 16 mg/g (gallic acid equivalents) and an antioxidant activity of 0.58 ± 0.04 µg/mL (trolox equivalents). HPLC analysis identified catechins (4.51 mg/g), gallic acid (3.2 mg/g) and epicatechins (0.88 mg/g) as the dominant phenolics. The extract was encapsulated in liposomes and hyalurosomes with a mean diameter of 148–159 nm, polydispersity index < 0.3, and zeta potentials of −47 to −44 mV, and remained stable for three months at 4 °C. In vitro studies showed that hyalurosomes significantly increased keratinocyte viability by up to 144% and provided better protection against oxidative stress compared to liposomes. A 12-week clinical study involving 40 volunteers was conducted to evaluate the efficacy of extract-loaded hyalurosomes as an “anti-aging serum” by assessing various skin parameters. This treatment resulted in improved skin hydration, a reduction in wrinkle depth, and a slight decrease in melanin and erythema levels as demonstrated by imaging. These results are promising for cosmeceutical applications using grape seed extract loaded in hyalurosomes.
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