Transdermal delivery of salvianolic acid B using thermosensitive hydrogel for the treatment of skin photoaging

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 28. doi: 10.1007/s00210-025-04411-5. Online ahead of print.

Abstract

Salvianolic acid B (Sal B) exhibits great potential in treating skin photoaging. However, its therapeutic activity is severely hindered by poor skin permeability, making the preparation of a transdermal formulation an urgent need. To overcome this limitation, the microwave method was employed to prepare chitosan-coated gold nanoparticles (CS-Au NPs), and the preparation process was optimized for co-encapsulation of Sal B and CS-Au NPs with hyaluronic acid and Pluronic F-127 (CAS@HF). Subsequently, the microscopic morphology and transdermal drug release capabilities of CAS@HF were evaluated using transmission electron microscopy and Franz diffusion cells, respectively. It was found that CAS@HF exhibited a fluid state at 25 °C and underwent gelation at 36.3 °C, forming a porous structure and demonstrating excellent skin permeability and retention. Furthermore, a photoaging cell model was established, and its anti-photoaging activity in vitro was assessed through CCK-8 assays, scratch assays, β-galactosidase staining, and Western blot analysis. It revealed that CAS@HF promoted cell migration, alleviated cellular senescence, and reduced ROS levels, which were associated with the inhibition of the P53/P21 pathway and the promotion of NRF2 translocation. Finally, a photoaging mouse model was constructed to further validate the anti-photoaging potential of CAS@HF in vivo using H&E staining, Masson's trichrome staining, and ROS staining. The results showed that CAS@HF mitigated photoaging phenomena, increased collagen levels and reduced ROS levels. In conclusion, CAS@HF enhanced the transdermal delivery of Sal B and potentiated its therapeutic effect on skin photoaging. This discovery provided potential therapeutic strategies and theoretical support for clinical treatment of photoaging.

Keywords: NRF2 nuclear translocation; P53/P21 pathway; Skin photoaging; Thermosensitivity; Transdermal delivery.