Methacrylated gelatin-based microneedles loaded with Polygonatum kingianum-derived extracellular vesicles for the protection against Ultraviolet B induced photoaging.

Ultraviolet B (UVB) exposure is a major extrinsic factor inducing skin photoaging, while conventional photoprotective strategies are often limited by insufficient skin penetration and poor compliance. In this study, a methacrylated gelatin (GelMA)-based microneedle system was developed for the efficient transdermal delivery of extracellular vesicles derived from Polygonatum kingianum (PkEVs) to prevent UVB-induced skin photoaging. The PkEVs exhibited a typical spherical morphology, with an average diameter of 168.2 ± 10.1 nm, and were successfully incorporated into a GelMA-based microneedle system (Pk@MN) for transdermal delivery. Pk@MN exhibited sufficient mechanical strength, with a breaking force of approximately 0.36 N per needle, and showed a rapid PkEV release profile, with approximately 90% of PkEVs released within 10 min. In vitro, Pk@MN effectively inhibited UVB-induced oxidative stress and cellular senescence in HaCaT cells, as indicated by reduced intracellular reactive oxygen species (ROS) levels and decreased senescence-associated β-galactosidase (SA-β-Gal) positive cells. Pk@MN also suppressed LPS-induced inflammatory responses in RAW264.7 cells. In vivo, pretreatment with Pk@MN markedly inhibited UVB-induced skin photoaging in mice, maintained skin elasticity by suppressing epidermal thickening, and promote dermal collagen deposition, with a 2.1-fold increase in collagen density compared with the Model group. Moreover, Pk@MN significantly suppressed the expression of the proinflammatory cytokine interleukin-6 (IL-6), approaching the level observed in the Control group. Transcriptome sequencing analysis further suggested that the protective effects of Pk@MN were associated with the regulation of pathways related to inflammation, oxidative stress, and tissue repair. This study highlights a GelMA-based microneedle platform for efficient transdermal delivery of plant-derived extracellular vesicles and provides a promising strategy for preventing UVB-induced skin photoaging.