Marquez-Lago Tatiana T, Allen Diana M, Thewalt Jenifer
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Theor Biol Med Model. 2010 Aug 17;7:33. doi: 10.1186/1742-4682-7-33.
The potential of using skin as an alternative path for systemically administering active drugs has attracted considerable interest, since the creation of novel drugs capable of diffusing through the skin would provide a great step towards easily applicable -and more humane- therapeutic solutions. However, for drugs to be able to diffuse, they necessarily have to cross a permeability barrier: the stratum corneum (SC), the uppermost set of skin layers. The precise mechanism by which drugs penetrate the skin is generally thought to be diffusion of molecules through this set of layers following a "tortuous pathway" around corneocytes, i.e. impermeable dead cells.
In this work, we simulate water transport and drug diffusion using a three-dimensional porous media model. Our numerical simulations show that diffusion takes place through the SC regardless of the direction and magnitude of the fluid pressure gradient, while the magnitude of the concentrations calculated are consistent with experimental studies.
Our results support the possibility for designing arbitrary drugs capable of diffusing through the skin, the time-delivery of which is solely restricted by their diffusion and solubility properties.
将皮肤作为全身给药活性药物的替代途径的潜力已引起了相当大的关注,因为能够透过皮肤扩散的新型药物的研发将朝着易于应用且更人道的治疗方案迈出重要一步。然而,药物要实现扩散,就必须穿过一个渗透屏障:角质层(SC),即皮肤最外层。一般认为,药物穿透皮肤的确切机制是分子沿着围绕角质形成细胞(即不可渗透的死细胞)的“曲折路径”通过这一层进行扩散。
在这项工作中,我们使用三维多孔介质模型模拟了水的传输和药物扩散。我们的数值模拟表明,无论流体压力梯度的方向和大小如何,扩散都通过角质层进行,同时计算出的浓度大小与实验研究结果一致。
我们的结果支持了设计能够透过皮肤扩散的任意药物的可能性,其定时释放仅受其扩散和溶解性的限制。