Abstract：
This paper studies the transport of monoclonal antibodies through skin tissue and initial lymphatics, which impacts the pharmacokinetics of monoclonal antibodies. Our model integrates a macroscale representation of the entire skin tissue with a mesoscale model that focuses on the papillary dermis layer. Our results indicate that it takes hours for the drugs to disperse from the injection site to the papillary dermis before entering the initial lymphatics. Additionally, we observe an inhomogeneous drug distribution in the interstitial space of the papillary dermis, with higher drug concentrations near initial lymphatics and lower concentrations near blood capillaries. To validate our model, we compare our numerical simulation results with experimental data, finding a good alignment. Our parametric studies on the drug molecule properties and injection parameters suggest that a higher diffusion coefficient increases the transport and uptake rate while binding slows down these processes. Furthermore, shallower injection depths lead to faster lymphatic uptake, whereas the size of the injection plume has a minor effect on the uptake rate. These findings advance our understanding of drug transport and lymphatic absorption after subcutaneous injection, offering valuable insights for optimizing drug delivery strategies and the design of biotherapeutics.
摘要：
本文研究了单克隆抗体通过皮肤组织和初始淋巴管的转运,影响单克隆抗体的药代动力学。我们的模型将整个皮肤组织的宏观表示与专注于乳头状真皮层的中尺度模型集成在一起。我们的结果表明，在进入初始淋巴管之前，药物需要数小时才能从注射部位分散到乳头状真皮。此外,我们观察到在乳头状真皮的间隙不均匀的药物分布，初始淋巴管附近的药物浓度较高，毛细血管附近的药物浓度较低。为了验证我们的模型，我们将数值模拟结果与实验数据进行了比较，找到一个好的对齐方式。我们对药物分子特性和注射参数的参数研究表明，较高的扩散系数会增加运输和摄取速率，而结合会减慢这些过程。此外，较浅的注射深度导致更快的淋巴吸收，而注射羽流的大小对摄取率影响较小。这些发现促进了我们对皮下注射后药物运输和淋巴吸收的理解，为优化药物输送策略和生物治疗设计提供有价值的见解。
