School of Mechanical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Biomech Model Mechanobiol. 2022 Dec;21(6):1825-1840. doi: 10.1007/s10237-022-01622-0. Epub 2022 Sep 3.
Subcutaneous injection of therapeutic monoclonal antibodies (mAbs) has gained increasing interest in the pharmaceutical industry. The transport, distribution and absorption of mAbs in the skin after injection are not yet well-understood. Experiments have shown that fibrous septa form preferential channels for fluid flow in the tissue. The majority of mAbs can only be absorbed through lymphatics which follow closely the septa network. Therefore, studying drug transport in the septa network is vital to the understanding of drug absorption. In this work, we present a mixed-dimensional multi-scale (MDMS) poroelastic model of adipose tissue for subcutaneous injection. More specifically, we model the fibrous septa as reduced-dimensional microscale interfaces embedded in the macroscale tissue matrix. The model is first verified by comparing numerical results against the full-dimensional model where fibrous septa are resolved using fine meshes. Then, we apply the MDMS model to study subcutaneous injection. It is found that the permeability ratio between the septa and matrix, volume capacity of the septa network, and concentration-dependent drug viscosity are important factors affecting the amount of drug entering the septa network which are paths to lymphatics. Our results show that septa play a critical role in the transport of mAbs in the subcutaneous tissue, and this role was previously overlooked.
皮下注射治疗性单克隆抗体（mAbs）在制药行业引起了越来越多的关注。但 mAbs 注射后在皮肤中的转运、分布和吸收仍未得到很好的理解。实验表明，纤维隔膜在组织中形成了优先的流体流动通道。大多数 mAbs 只能通过淋巴管吸收，而淋巴管与隔膜网络密切相关。因此，研究隔膜网络中的药物输送对于理解药物吸收至关重要。在这项工作中，我们提出了一种用于皮下注射的脂肪组织混合维多尺度（MDMS）多孔弹性模型。更具体地说，我们将纤维隔膜建模为嵌入宏观组织基质中的降维微尺度界面。该模型首先通过将纤维隔膜用细网格解析的全维模型的数值结果进行比较来验证。然后，我们将 MDMS 模型应用于皮下注射研究。结果表明，隔膜与基质之间的渗透比、隔膜网络的体积容量以及浓度依赖性药物粘度是影响进入隔膜网络的药物量的重要因素，而这些药物是通往淋巴管的途径。我们的研究结果表明，隔膜在 mAbs 在皮下组织中的转运中起着关键作用，而这一作用之前被忽视了。
