Modeling the Percutaneous Absorption of Solvent-deposited Solids Over a Wide Dose Range
Modeling the Percutaneous Absorption of Solvent-deposited Solids Over a Wide Dose Range
复制标题
模拟宽剂量范围内溶剂沉积固体的经皮吸收
DOI：
10.1016/j.xphs.2021.10.001
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：
Yu, Fang;Tonnis, Kevin;Xu, Lijing;Jaworska, Joanna;Kasting, Gerald B.
两种护肤剂烟酰胺(烟酰胺，NA)和烟酸甲酯(MN)，安装在Franz扩散池中，以溶剂沉积在体外人皮肤上，根据最近发表的皮肤渗透力学模型的新变化(Yu等人)，分析了两种护肤剂的瞬时吸收。2020年。J医药科学110：2149-56)。该模型遵循两种成分的吸收和蒸发，即溶质和溶剂，它既包括毛囊运输成分，也包括沉积在皮肤上的高熔点、亲水性固体的溶解速度限制。介绍了改进溶剂法沉积固体的瞬时扩散模拟的显式算法。模拟可以解释NA和MN在超过4.5个数量级的剂量范围内的体外皮肤渗透时间过程。该模型允许人们在机理的基础上描述为什么NA的经皮吸收速率比其更低熔点、更亲油的类似物MN的透皮吸收速率低约60倍。这进一步表明，MN扰乱角质层屏障脂类并增加其通透性，而NA不会，这对从事模拟生物脂屏障的分子模型师提出了挑战。
The transient absorption of two skin care agents, niacinamide (nicotinamide, NA) and methyl nicotinate (MN), solvent-deposited on ex vivo human skin mounted in Franz diffusion cells has been analyzed according to a new variation on a recently published mechanistic skin permeability model (Yu et al. 2020. J Pharm Sci 110:2149-56). The model follows the absorption and evaporation of two components, solute and solvent, and it includes both a follicular transport component and a dissolution rate limitation for high melting, hydrophilic solids deposited on the skin. Explicit algorithms for improving the simulation of transient diffusion of solvent-deposited solids are introduced. The simulations can account for the ex vivo skin permeation time course of both NA and MN over a dose range exceeding 4.5 orders of magnitude. The model allows one to describe on a mechanistic basis why the percutaneous absorption rate of NA is approximately 60-fold lower than that of its lower melting, more lipophilic analog, MN. It furthermore suggests that MN perturbs stratum corneum barrier lipids and increases their permeability while NA does not, presenting a challenge to molecular modelers engaged in simulating biological lipid barriers.