PEG-400-Modified Transethosomes for Resveratrol Delivery: Enhanced Dermal Penetration and Collagen Remodeling over...

Skin aging is a complex biological process driven by collagen degradation and oxidative damage, often exacerbated by UV exposure. While resveratrol is a premier antioxidant for anti-aging, its topical efficacy is historically limited by poor water solubility and weak skin penetration. This study addresses these barriers by developing optimized polyethylene glycol-based liposomes (PEG-liposomes) as novel deformable liposome derivative. The uncoated vesicles demonstrated high stability and uniformity, with a size of 320.17 ± 0.25 nm and a zeta potential of -35.2 ± 0.4 mV. By coating these vesicles with 0.1% hyaluronic acid (HA), successful surface functionalization and improved size stability was achieved. Ex vivo and confocal studies confirmed that these PEG-liposomes successfully reached the deep dermis; notably, a sequential application strategy of the coated and uncoated PEG-liposomes showed that uncoated vesicles could transiently disrupt lipid structures to facilitate deeper penetration for the HA-coated versions. When integrated with micro-needling via a derma roller, the system triggered significant collagen remodeling and a surge in antioxidant enzymes like SOD, while simultaneously reducing oxidative stress markers such as MDA, MMP-1, and the aging indicator beta-galactosidase. The cooperative effect of this dual-vesicle system not only restored the structural integrity of the dermal-epidermal junction but also significantly outperformed existing commercial resveratrol products. Our findings demonstrate that this novel PEG-liposomal system provides a transformative approach to deep-tissue rejuvenation. Through its unique synergistic mechanism with micro-needling, it achieves biological remodeling and dermal restoration that surpasses the efficacy of current market-leading standards.