Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Drug Des Devel Ther. 2023 May 26;17:1593-1609. doi: 10.2147/DDDT.S397541. eCollection 2023.
As a keratolytic, salicylic acid (SA) can be topically applied in various formulations and doses in dermatology. Supramolecular SA hydrogel, a new SA formulation with higher bioavailability, is developed and commercially available nowadays. However, there still remain concerns that the long-term and continual application of SA at low concentrations may jeopardize the cutaneous barrier properties.
To reveal the long-term effects of 0.5-5% supramolecular SA hydrogel on the skin barrier in normal mice models.
The 0.5%, 1%, 2%, and 5% supramolecular SA hydrogel or hydrogel vehicle without SA was applied to mice's shaved dorsal skin once per day respectively. Tissue samples of the dorsal skin were harvested on day 14 and 28 of the serial application of SA for histopathological observation and transcriptomic analysis.
Following topical supramolecular SA hydrogel therapy with various concentrations of SA (0.5%, 1%, 2%, and 5%) for 14 days and 28 days, there were no obvious macroscopic signs of impaired cutaneous health and no inflammatory or degenerative abnormalities were observed in histological results. Additionally, the transcriptomic analysis revealed that on day 14, SA dramatically altered the expression of genes related to the extracellular matrix structural constituent. And on day 28, SA regulated gene expression profiles of keratinization, cornified envelope, and lipid metabolism remarkably. Furthermore, the expression of skin barrier related genes was significantly elevated after the application of SA based on RNA-seq results, and this is likely to be associated with the PPAR signaling pathway according to the enrichment analysis.
Our findings demonstrated that the sustained topical administration of the 0.5-5% supramolecular SA hydrogel for up to 28 days did no harm to normal murine skin and upregulated the expression of genes related to the epidermal barrier.
作为一种角质松解剂，水杨酸（SA）可以在皮肤科中以各种制剂和剂量局部应用。目前已经开发出并商业化了一种具有更高生物利用度的新型 SA 制剂——超分子 SA 水凝胶。然而，人们仍然担心长期和持续使用低浓度的 SA 可能会损害皮肤屏障功能。
揭示 0.5%-5%超分子 SA 水凝胶在正常小鼠模型中对皮肤屏障的长期影响。
将 0.5%、1%、2%和 5%的超分子 SA 水凝胶或不含 SA 的水凝胶载体分别每天一次涂抹于小鼠剃毛背部皮肤。在连续应用 SA 的第 14 天和第 28 天，采集背部皮肤组织样本进行组织病理学观察和转录组分析。
在连续应用不同浓度（0.5%、1%、2%和 5%）超分子 SA 水凝胶治疗 14 天和 28 天后，局部外用超分子 SA 水凝胶治疗未见明显的皮肤健康受损的宏观迹象，组织学结果也未观察到炎症或退行性异常。此外，转录组分析显示，在第 14 天，SA 显著改变了与细胞外基质结构成分相关的基因表达。在第 28 天，SA 显著调节了角化、角蛋白包膜和脂质代谢相关的基因表达谱。此外，根据 RNA-seq 结果，应用 SA 后皮肤屏障相关基因的表达显著上调，这可能与 PPAR 信号通路有关。
我们的研究结果表明，持续 28 天局部应用 0.5%-5%超分子 SA 水凝胶对正常小鼠皮肤没有伤害，并上调了与表皮屏障相关的基因表达。
