Wu Lili, Tao Yue, Xu Yi, Liang Zexu, Zhao Yu
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230002, Anhui, China.
Department of Plastic Surgery, Anhui Victoria Plastic Surgery Hospital, Hefei, 230002, Anhui, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 28. doi: 10.1007/s00210-025-04411-5.
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.
丹酚酸B（Sal B）在治疗皮肤光老化方面具有巨大潜力。然而，其治疗活性因皮肤渗透性差而受到严重阻碍，因此迫切需要制备透皮制剂。为克服这一局限性，采用微波法制备壳聚糖包被的金纳米颗粒（CS-Au NPs），并对制备过程进行优化，将Sal B和CS-Au NPs与透明质酸和普朗尼克F-127共包封（CAS@HF）。随后，分别使用透射电子显微镜和Franz扩散池评估CAS@HF的微观形态和透皮药物释放能力。结果发现，CAS@HF在25℃时呈流体状态，在36.3℃时发生凝胶化，形成多孔结构，并表现出优异的皮肤渗透性和滞留性。此外，建立了光老化细胞模型，并通过CCK-8测定、划痕试验、β-半乳糖苷酶染色和蛋白质印迹分析评估其体外抗光老化活性。结果表明，CAS@HF促进细胞迁移，减轻细胞衰老，并降低ROS水平，这与抑制P53/P21途径和促进NRF2易位有关。最后，构建光老化小鼠模型，使用苏木精-伊红染色、Masson三色染色和ROS染色进一步验证CAS@HF在体内的抗光老化潜力。结果表明，CAS@HF减轻了光老化现象，增加了胶原蛋白水平并降低了ROS水平。总之，CAS@HF增强了Sal B的透皮递送，并增强了其对皮肤光老化的治疗效果。这一发现为光老化的临床治疗提供了潜在的治疗策略和理论支持。
