A Framework for Incorporating Transient Solute-Keratin Binding Into Dermal Absorption Models
A Framework for Incorporating Transient Solute-Keratin Binding Into Dermal Absorption Models
复制标题
将瞬时溶质-角蛋白结合纳入真皮吸收模型的框架
DOI：
10.1016/j.xphs.2021.11.026
复制
发表时间：
2022
影响因子：
3.8
通讯作者：
Kasting, Gerald B.
中科院分区：
文献类型：
--
作者：
Nitsche, Johannes M.;Kasting, Gerald B.
分析和讨论了涉及瞬时溶质结合分离角蛋白底物的实验的解释，根据它们对局部应用化合物通过人体角质层的瞬时渗透的影响。该分析建立在早期模型（Nitsche和Frasch 2011 Chem Eng Sci 66:2019-41）的基础上，在微观到宏观转换之前增加了第二级均质化（超声到微观）。这里的“超镜”指的是分离的角蛋白悬浮液，“微观”指的是角质层的角质细胞内部，“宏观”指的是角质层的组织平均特性。结果在当前超声结合参数化的背景下进行解释。目前的分析仅限于稀溶液中常见的线性结合等温线，揭示了宏观正向结合速率常数作为溶质亲脂性函数的最大值，而潜在的平衡常数单调增加，宏观反向结合速率常数单调降低。最大值的大小和位置取决于角质层的水化状态。表达这些发现的显式方程允许将分离角蛋白的平衡和动力学结合数据应用于通过皮肤的瞬时吸收动力学。它们将使人们能够对长期以来公认的角质层储层功能进行更定量的估计。
Interpretation of experiments involving transient solute binding to isolated keratin substrates is analyzed and discussed in terms of their impact on transient permeation of topically-applied compounds through human stratum corneum. The analysis builds upon an earlier model (Nitsche and Frasch 2011 Chem Eng Sci 66:2019-41) by adding a second level of homogenization (ultrascopic-to-microscopic) prior to the microscopic-to-macroscopic conversion. Here “ultrascopic” refers to isolated keratin suspensions, “microscopic” to corneocyte interiors and “macroscopic” to tissue-averaged properties in the stratum corneum. Results are interpreted in the context of current parameterizations of the underlying ultrascopic binding parameters. The present analysis, which is limited to linear binding isotherms common in dilute solutions, reveals a maximum in the macroscopic forward binding rate constant as a function of solute lipophilicity, whereas the underlying equilibrium constant increases monotonically and the macroscopic reverse binding rate constant decreases monotonically. The size and location of the maximum depends upon the hydration state of the stratum corneum. Explicit equations expressing these findings allow both equilibrium and kinetic binding data in isolated keratins to be applied to the kinetics of transient absorption through the skin. They will enable more quantitative estimation of the long-recognized stratum corneum reservoir function.