School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States.
School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States.
Int J Pharm. 2024 Aug 15;661:124419. doi: 10.1016/j.ijpharm.2024.124419. Epub 2024 Jul 6.
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.
本文研究了单克隆抗体通过皮肤组织和初始淋巴管的传输，这对单克隆抗体的药代动力学有影响。我们的模型将整个皮肤组织的宏观表示与专注于乳头真皮层的介观模型相结合。我们的结果表明，药物需要数小时才能从注射部位扩散到乳头真皮层，然后进入初始淋巴管。此外，我们观察到在乳头真皮间质空间中存在药物分布不均匀的现象，靠近初始淋巴管的药物浓度较高，靠近毛细血管的药物浓度较低。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，发现吻合良好。我们对药物分子性质和注射参数的参数研究表明，较高的扩散系数会增加药物的传输和摄取速率，而结合会减缓这些过程。此外，较浅的注射深度会导致更快的淋巴摄取，而注射羽流的大小对摄取速率的影响较小。这些发现提高了我们对皮下注射后药物传输和淋巴吸收的理解，为优化药物输送策略和生物治疗药物的设计提供了有价值的见解。
