Manager, Computational Medicine and Biology, CFD Research Corporation, Huntsville, AL 35806, United States.
Manager, Computational Medicine and Biology, CFD Research Corporation, Huntsville, AL 35806, United States.
Eur J Pharm Sci. 2021 Dec 1;167:105924. doi: 10.1016/j.ejps.2021.105924. Epub 2021 Jul 18.
The delivery of therapeutic drugs through the skin is a promising alternative to oral or parenteral delivery routes because dermal drug delivery systems (DSs) offer unique advantages, such as controlled drug release over sustained periods and a significant reduction in first-pass effects, thus reducing the required dosing frequency and the level of patient noncompliance. Furthermore, DSs find applications in multiple therapeutic areas, including drug repurposing. This article presents an integrated biophysical model of dermal absorption for simulating the permeation and absorption of compounds delivered transdermally. The biophysical model is physiologically/biologically inspired and combines a holistic model of healthy skin with whole-body physiology-based pharmacokinetics through the dermis microcirculation. The model also includes the effects of chemical penetration enhancers and hair follicles on transdermal transport. The model-predicted permeation and pharmacokinetics of select compounds were validated using in vivo data reported in the literature. We conjecture that the integrated model can be used to gather insights into the permeation and systemic absorption of transdermal formulations (including cosmetic products) released from novel depots and to optimize delivery systems. Furthermore, the model can be extended to diseased skin with parametrization and structural adjustments specific to skin diseases.
通过皮肤输送治疗药物是一种有前途的替代口服或肠胃外给药途径的方法，因为皮肤药物输送系统（DS）具有独特的优势，例如可以在持续时间内控制药物释放，并显著减少首过效应，从而减少所需的给药频率和患者不遵医嘱的程度。此外，DS 在多个治疗领域都有应用，包括药物再利用。本文提出了一种综合的皮肤吸收生物物理模型，用于模拟经皮给药化合物的渗透和吸收。该生物物理模型受生理/生物学启发，通过皮肤真皮微循环将健康皮肤的整体模型与基于全身生理学的药代动力学相结合。该模型还包括化学渗透增强剂和毛囊对经皮传递的影响。使用文献中报道的体内数据验证了模型预测的选择化合物的渗透和药代动力学。我们推测，该综合模型可用于深入了解从新型制剂（包括化妆品）中释放的经皮制剂的渗透和全身吸收，并优化输送系统。此外，该模型可以通过针对皮肤病的参数化和结构调整扩展到患病皮肤。
