Döge Nadine, Avetisyan Araks, Hadam Sabrina, Pfannes Eva Katharina Barbosa, Rancan Fiorenza, Blume-Peytavi Ulrike, Vogt Annika
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Eur J Pharm Biopharm. 2017 Jul;116:138-148. doi: 10.1016/j.ejpb.2016.12.012. Epub 2016 Dec 21.
Topical dermatotherapy is intended to be used on diseased skin. Novel drug delivery systems even address differences between intact and diseased skin underlining the need for pre-clinical assessment of different states of barrier disruption. Herein, we studied how short-term incubation in culture media compared to incubation in humidified chambers affects human skin barrier function and viability. On both models we assessed different types and intensities of physical and chemical barrier disruption methods with regard to structural integrity, biophysical parameters and cytokine levels. Tissue degeneration and proliferative activity limited the use of tissue cultures to 48h. Viability is better preserved in cultured tissue. Tape-stripping (50×TS) and 4h sodium lauryl sulfate (SLS) pre-treatment were identified as highly reproducible and effective procedures for barrier disruption. Transepidermal water loss (TEWL) values reproducibly increased with the intensity of disruption while sebum content and skin surface pH were of limited value. Interleukin (IL)-6/8 and various chemokines and proteases were increased in tape-stripped skin which was more pronounced in SLS-treated skin tissue extracts. Thus, albeit limited to 48h, cultured full-thickness skin maintained several barrier characteristics and responded to different intensities of barrier disruption. Potentially, these models can be used to assess pre-clinically the efficacy and penetration of anti-inflammatory compounds.
局部皮肤疗法旨在用于患病皮肤。新型药物递送系统甚至解决了完整皮肤和患病皮肤之间的差异，强调了对不同屏障破坏状态进行临床前评估的必要性。在此，我们研究了与在加湿箱中孵育相比，在培养基中短期孵育如何影响人体皮肤屏障功能和活力。在这两种模型上，我们评估了不同类型和强度的物理和化学屏障破坏方法对结构完整性、生物物理参数和细胞因子水平的影响。组织退化和增殖活性将组织培养的使用限制在48小时。在培养的组织中，活力得到更好的保留。胶带剥离（50次）和4小时十二烷基硫酸钠（SLS）预处理被确定为屏障破坏的高度可重复且有效的程序。经表皮水分流失（TEWL）值随破坏强度可重复增加，而皮脂含量和皮肤表面pH值的价值有限。白细胞介素（IL）-6/8以及各种趋化因子和蛋白酶在胶带剥离的皮肤中增加，在SLS处理的皮肤组织提取物中更为明显。因此，尽管限于48小时，但培养的全层皮肤保持了几种屏障特征，并对不同强度的屏障破坏做出反应。这些模型有可能用于临床前评估抗炎化合物的疗效和渗透性。
