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Development of fibrin hydrogel–based in vitro bioassay system for assessment of skin permeability to and pro-inflammatory activity mediated by zinc ion released from nanoparticles
Analytical and Bioanalytical Chemistry ( IF 3.8 ) Pub Date : 2020-10-06 , DOI: 10.1007/s00216-020-02970-5
Yosuke Tabei , Waka Lin , Shusaku Shiomoto , Tomoaki Nakayama , Akinari Sonoda , Masanori Horie

Nanoparticles (NPs) are promising products in industry and medicine due to their unique physicochemical properties. In particular, zinc oxide (ZnO) NPs are extensively incorporated into sunscreens to protect the skin from exposure to ultraviolet radiation. However, there are several health concerns about skin penetration and the resultant toxicity. As methodologies for evaluating NP toxicity are under development, it is difficult to fully assess the toxicity of ZnO NPs toward humans. In this study, we developed a platform to simultaneously detect skin permeability to and pro-inflammatory activity mediated by zinc ion released from NPs. First, we generated a stable reporter cell line expressing green fluorescent protein (GFP) under the control of interleukin-8 (IL-8) promoter activity. The expression levels of GFP induced by zinc reflected the endogenous IL-8 expression levels and the pro-inflammatory responses. Next, we found that fibrin hydrogel can reproduce permeability to zinc ion of a human skin equivalent model and is therefore a promising material to assess skin permeability to zinc ion. Then, we constructed a fibrin hydrogel–based in vitro bioassay system for the simultaneous detection of skin permeability to and pro-inflammatory activity mediated by zinc ion released from NPs by using a stable reporter cell line and a fibrin hydrogel layer. This bioassay system is a promising in vitro permeation test due to its technical simplicity and good predictability. Overall, we believe that our bioassay system can be widely used in the cosmetics and pharmaceutical industries.



中文翻译:

基于纤维蛋白水凝胶的体外生物测定系统的开发,用于评估纳米粒子释放的锌离子介导的皮肤通透性和促炎活性

纳米颗粒(NPs)由于其独特的物理化学特性,在工业和医学上都是有前途的产品。尤其是,氧化锌(ZnO)NP广泛掺入防晒霜中,以保护皮肤免受紫外线辐射。然而,关于皮肤渗透及其产生的毒性存在一些健康问题。由于评估NP毒性的方法正在开发中,因此难以全面评估ZnO NP对人体的毒性。在这项研究中,我们开发了一个平台来同时检测由NP释放的锌离子介导的皮肤通透性和促炎活性。首先,我们在白介素8(IL-8)启动子活性的控制下生成了稳定的表达绿色荧光蛋白(GFP)的报告细胞系。IL-8表达水平和促炎反应。接下来,我们发现纤维蛋白水凝胶可以复制人皮肤等效模型对锌离子的渗透性,因此是评估皮肤对锌离子渗透性的有前途的材料。然后,我们构建了基于纤维蛋白水凝胶的体外生物测定系统,通过使用稳定的报告细胞系和纤维蛋白水凝胶层,同时检测由NP释放的锌离子介导的皮肤通透性和促炎活性。该生物测定系统由于其技术简单性和良好的可预测性而成为有希望的体外渗透测试。总体而言,我们相信我们的生物测定系统可以广泛用于化妆品和制药行业。

更新日期:2020-11-23
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