Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.
Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.
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DOI：
10.1016/j.jconrel.2017.05.034
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发表时间：
2017-08-28
期刊：
影响因子：
--
通讯作者：
Frasch HF
中科院分区：
文献类型：
--
作者：
Barbero AM;Frasch HF
角质层的复杂结构对透皮渗透的影响尚未被现有模型完全描述。定量和深入的研究皮肤渗透是必不可少的化学品暴露评估和药物的透皮给药。本研究的目的是分析异质性、各向异性、不对称性、滤泡扩散和主要扩散屏障位置对经皮渗透的影响。在目前的研究中，通过一个二维各向异性的砖和砂浆的角质层的几何形状的瞬态扩散的解决方案是使用商业有限元程序COMSOL Multiphysics。首先，使用等效多层几何形状的解析解来确定脂质或角质细胞是否构成主要的渗透屏障。这些解析解也被应用于有限元解的验证。在这些部分中分析了三种示例性化合物：邻苯二甲酸二乙酯、咖啡因和尼古丁。然后，使用咖啡因作为说明性化合物研究了深度和卵泡扩散的不对称性。研究结果表明：主要的渗透屏障位于脂质层中，通过砖和灰泥几何结构的扩散通量和延迟时间与多层几何结构的值几乎相同，当脂质跨双层扩散系数或分配系数随深度变化时，通量和延迟时间受到影响，但不受深度依赖的角质细胞扩散系数的影响;并且毛囊的贡献对于低的跨双层脂质扩散率具有重要意义，特别是当涉及毛囊和周围角质层之间的流量时。这项研究表明，扩散主要是跨细胞和主要的障碍是位于脂质层。
The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers.
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影响因子：
6.5
作者：
BOUWSTRA, JA;GOORIS, GS;BRAS, W
通讯作者：
BRAS, W
影响因子：
3.7
作者：
Chen, Longjian;Lian, Guoping;Han, Lujia
通讯作者：
Han, Lujia
影响因子：
64.8
作者：
COHEN, BE;BANGHAM, AD
通讯作者：
BANGHAM, AD
DOI：
10.1088/0508-3443/14/12/307
发表时间：
1963-01-01
期刊：
BRITISH JOURNAL OF APPLIED PHYSICS
影响因子：
--
作者：
ASH, R;BARRER, RM;PETROPOULOS, JH
通讯作者：
PETROPOULOS, JH
影响因子：
9.5
作者：
BERNER, B;COOPER, ER
通讯作者：
COOPER, ER