Impact of solvent dry down, vehicle pH and slowly reversible keratin binding on skin penetration of cosmetic relevant compounds: I. Liquids
Impact of solvent dry down, vehicle pH and slowly reversible keratin binding on skin penetration of cosmetic relevant compounds: I. Liquids
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溶剂干燥、载体 pH 值和缓慢可逆角蛋白结合对化妆品相关化合物皮肤渗透的影响： I. 液体
DOI：
10.1016/j.ijpharm.2022.122030
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发表时间：
2022
影响因子：
5.8
通讯作者：
Kasting, Gerald B.
中科院分区：
文献类型：
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作者：
Tonnis, Kevin;Nitsche, Johannes M.;Xu, Lijing;Haley, Alison;Jaworska, Joanna;Kasting, Gerald B.
为了测量最新的UB/UC/P&G皮肤渗透模型的进展和评估其性能，我们模拟了从化妆品相关化合物的溶剂沉积研究中获得的有限剂量体外人皮肤渗透数据的18种化合物子集（休伊特等人，应用毒理学杂志2019，1-13）。最近的模型扩展涉及溶质与角质层角蛋白的缓慢可逆结合。所选择的子集是在皮肤温度下为液体的化合物。选择这一组是为了区分影响固相化合物的缓慢结合和缓慢溶解效应。为了充分模拟物理实验，需要调整蒸发传质系数，以更好地代表研究中使用的扩散池系统。在此调整后，该模型成功地预测了18种化合物中的12种的经皮递送和皮肤表面分布。给药溶液中的半胱氨酸反应性、高度水溶性或高度离子化的化合物。如目前参数化的，与角蛋白的缓慢结合显示出显著改变角质层动力学和扩散滞后时间，但不是数据集中更亲脂性化合物的最终处置。提出了进一步改进建模方法和实验设计的建议。
To measure progress and evaluate performance of the newest UB/UC/P&G skin penetration model we simulated an 18-compound subset of finite dose in vitro human skin permeation data taken from a solvent-deposition study of cosmetic-relevant compounds (Hewitt et al., J. Appl. Toxicol. 2019, 1–13). The recent model extension involved slowly reversible binding of solutes to stratum corneum keratins. The selected subset was compounds that are liquid at skin temperature. This set was chosen to distinguish between slow binding and slow dissolution effects that impact solid phase compounds. To adequately simulate the physical experiments there was a need to adjust the evaporation mass transfer coefficient to better represent the diffusion cell system employed in the study. After this adjustment the model successfully predicted both dermal delivery and skin surface distribution of 12 of the 18 compounds. Exceptions involved compounds that were cysteine-reactive, highly water-soluble or highly ionized in the dose solution. Slow binding to keratin, as presently parameterized, was shown to significantly modify the stratum corneum kinetics and diffusion lag times, but not the ultimate disposition, of the more lipophilic compounds in the dataset. Recommendations for further improvement of both modeling methods and experimental design are offered.