In Silico Prediction of Percutaneous Absorption and Disposition Kinetics of Chemicals
In Silico Prediction of Percutaneous Absorption and Disposition Kinetics of Chemicals
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DOI：
10.1007/s11095-014-1575-0
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发表时间：
2015-05-01
影响因子：
3.7
通讯作者：
Lian, Guoping
中科院分区：
文献类型：
--
作者：
Chen, Longjian;Han, Lujia;Lian, Guoping
开发预测化学物质在皮肤层中的经皮吸收和处置动力学的计算机模型，以促进经皮给药系统和护肤产品的设计，以及职业或消费者暴露的风险评估。建立了一个通用的计算机模型来模拟皮肤在角质层、活真皮和真皮层中的渗透、吸收和处置动力学。通过考虑分子在皮肤层中的分配、结合和迁移，提出了确定化学物质分配和扩散特性的方程。采用12种化学物质的体外皮肤渗透数据对模型进行验证。比较了12种被试化学物质在皮肤层中的渗透和分布情况。对于大多数被测化学品，实验和模型结果与决定系数> 0.80和相对均方根误差< 1.20一致。活性表皮和真皮中最大浓度和曲线下面积的配置动力学参数随着疏水性的增加而增加，但随着疏水性的进一步增加而达到最大值，然后下降。通过考虑皮肤的生理结构和组成，确定化学物质在皮肤层中的分配和扩散特性。这允许在硅模拟经皮渗透，吸收和处置动力学的广泛的化学空间。该模型产生的结果与12种化学物质的实验数据非常吻合，表明该框架大大改进，可支持药物和化妆品活性物质的经皮输送以及综合风险评估。
To develop in-silico model for predicting percutaneous absorption and disposition kinetics of chemicals in skin layers so as to facilitate the design of transdermal drug delivery systems and skin care products, and risk assessment of occupational or consumer exposure.A general-purpose computer model for simulating skin permeation, absorption and disposition kinetics in the stratum corneum, viable dermis and dermis has been developed. Equations have been proposed for determining the partition and diffusion properties of chemicals by considering molecular partition, binding and mobility in skin layers. In vitro skin penetration data of 12 chemicals was used to validate the model.The observed and simulated permeation and disposition in skin layers were compared for 12 tested chemicals. For most tested chemicals, the experimental and model results are in good agreement with the coefficient of determination > 0.80 and relative root mean squared error < 1.20. The disposition kinetic parameters of the maximum concentration and the area under the curve in the viable epidermis and dermis initially increased with hydrophobicity, but reached maxima and then decreased with further increase of hydrophobicity.By considering skin physiological structure and composition, the partition and diffusion properties of chemicals in skin layers are determined. This allows in-silico simulation of percutaneous permeation, absorption and disposition kinetics of wide chemical space. The model produced results in good agreement with experimental data of 12 chemicals, suggesting a much improved framework to support transdermal delivery of drug and cosmetic actives as well as integrated risk assessment.