The objective of this study was to evaluate the response of the rat epidermal keratinocyte organotypic culture (ROC) to permeation enhancers, and to compare these responses to those in human cadaver skin. Different concentrations of two mixtures for enhancing permeation were investigated, sodium dodecyl sulfate:phenyl piperazine and methyl pyrrolidone:dodecyl pyridinium chloride, using skin impedance spectroscopy and two experimental compounds, the lipophilic corticosterone and the hydrophilic sucrose. The chemical irritation effects of the formulations were evaluated based on leakage of lactate dehydrogenase enzyme (LDH) and cellular morphological perturbation. This study provides evidence for direct correlations of permeation/permeation, impedance/impedance and permation/impedance between the culture model and human skin. The only exception was the enhancer induced permeation of sucrose which was 1-40-fold higher in ROC compared to human skin, reflecting the more disordered lipid organization in stratum corneum and consequently the greater number of polar pathways. LDH leakage and cellular morphology indicated that it was possible to differentiate between safe permeation enhancers from irritating agents. This is not only the first study to have compared the enhancer effects on a cultured skin model with human skin, but also it has demonstrated enhancer induced irritation using an artificial skin model.

译文

:这项研究的目的是评估大鼠表皮角质形成细胞器官型培养(ROC)对渗透促进剂的反应,并将这些反应与人体尸体皮肤的反应进行比较。使用皮肤阻抗光谱法和两种实验化合物脂溶性皮质酮和亲水性蔗糖,研究了十二烷基硫酸钠:苯基哌嗪钠和甲基吡咯烷酮:十二烷基吡啶鎓氯化物的两种不同浓度的混合物,以提高渗透性。基于乳酸脱氢酶(LDH)的泄漏和细胞形态扰动来评估制剂的化学刺激作用。这项研究提供了文化模型与人体皮肤之间渗透/渗透,阻抗/阻抗和渗透/阻抗直接相关的证据。唯一的例外是增强剂诱导的蔗糖渗透率在ROC中是人皮肤的1-40倍,这反映了角质层中脂质组织的紊乱程度更大,因此极性途径的数量也更多。 LDH泄漏和细胞形态表明,可以区分安全性增强剂和刺激性剂。这不仅是将人​​皮肤对培养的皮肤模型的增强效果进行比较的第一项研究,而且还证明了使用人工皮肤模型对增强剂引起的刺激作用。

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