Anti-Photoaging Effect of Soluble Microneedles Loaded with Hydroxytyrosol

Skin photoaging, marked by structural and functional changes, is mainly caused by long-term ultraviolet (UV) exposure. This study sought to create hydroxytyrosol (HT)-loaded soluble microneedles (HT MNs) and thoroughly assess their anti-photoaging effects and underlying mechanisms in vitro and in vivo. The optimized HT MNs, featuring tips with 10% HT + 5% hyaluronic acid (HA) and a backing layer of 10% polyvinyl pyrrolidone (PVP), demonstrated robust mechanical strength (withstanding an axial force of 10 N without fracture), adequate penetration depth (>200 μm), and efficient skin self-recovery post-removal. In vitro, HT MNs notably boosted cell viability, reduced reactive oxygen species (ROS) levels, and suppressed senescence-associated β-galactosidase (A-β-Gal) expression in UVA-exposed human skin fibroblasts (HSF). In vivo, in a UVA + UVB-irradiated mouse model, HT MNs significantly enhanced skin hydration and elasticity, increased collagen density (confirmed by Masson staining), decreased malondialdehyde (MDA) content, and elevated the activities of glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-Px). Western blot analysis further revealed that HT MNs upregulated the expression of collagen type I alpha 1 (COL1A1), elastin (ELN), hyaluronan synthase 2 (HAS2), and filaggrin (FLG), while downregulating matrix metalloproteinase 1. Overall, these findings suggest that HT MNs effectively mitigate UV-induced photoaging through antioxidant, anti-senescence, and extracellular matrix (ECM)-regulating mechanisms, underscoring their potential as a novel transdermal anti-photoaging therapy.