School of Environment and Science, Griffith University, Gold Coast, Queensland 4222, Australia.
School of Environment and Science, Griffith University, Gold Coast, Queensland 4222, Australia; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia.
Int J Pharm. 2019 Oct 5;569:118547. doi: 10.1016/j.ijpharm.2019.118547. Epub 2019 Aug 1.
The stratum corneum is the main barrier to transdermal drug delivery which has previously resulted in mathematical modelling of solute transport in the skin being primarily directed at this skin layer. However, for topical treatment and skin toxicity studies, the concentration in the epidermis and dermis is important and needs to be modelled mathematically. Hitherto, mathematical models for viable skin layers typically simplified the clearance of solute by blood, either assuming sink condition at the top of the skin capillary loops or assuming a distributed clearance in the dermis. This paper is an attempt to develop a physiologically based mathematical model of drug transport in the viable skin. It incorporates explicit modelling of the capillary loops within the dermis and employs COMSOL Multiphysics® software to model the transport in three dimensions. Previously derived simplified models were compared to the results from this new numerical model. The results of this comparison showed that the simplified model reasonably described the average concentration in the viable skin layers when parameters of the models were chosen appropriately. When the recruitment of the capillary loops in the dermis was full and the top of capillary loops was at a depth of 100μm, the effective depth to place a sink condition in the simpler models was found to be at 150μm. However, when there was only partial recruitment of the capillaries, the effective depth increased to 180μm. The presented modelling is also essential for determining a transdermal flux when the stratum corneum barrier is compromised by such methods as microporation, application of chemical enhancers or microneedles.
角质层是经皮药物递送的主要屏障，这导致此前溶质在皮肤中的传输的数学模型主要针对这一皮肤层。然而，对于局部治疗和皮肤毒性研究，表皮和真皮中的浓度很重要，需要进行数学建模。迄今为止，针对活的皮肤层的数学模型通常通过血液简化溶质的清除，要么假设在皮肤毛细血管环的顶部处于吸收状态，要么假设在真皮中存在分布清除。本文试图开发一种药物在活的皮肤中传输的基于生理学的数学模型。它明确地对真皮中的毛细血管环进行建模，并使用 COMSOL Multiphysics®软件对三维传输进行建模。将之前推导的简化模型与来自这个新的数值模型的结果进行了比较。该比较的结果表明，当模型的参数选择合适时，简化模型可以合理地描述活的皮肤层中的平均浓度。当真皮中的毛细血管环充分募集并且毛细血管环的顶部位于 100μm 的深度时，发现将吸收状态置于更简单的模型中的有效深度为 150μm。然而，当只有部分毛细血管募集时，有效深度增加到 180μm。所呈现的模型对于确定经皮通量也很重要，当角质层屏障通过微穿孔、化学增强剂或微针等方法受到损害时。
