School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, United States of America.
School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, United States of America.
Microvasc Res. 2022 Jan;139:104228. doi: 10.1016/j.mvr.2021.104228. Epub 2021 Sep 20.
The subcutaneous injection has emerged to become a feasible self-administration practice for biotherapeutics due to the patient comfort and cost-effectiveness. However, the available knowledge about transport and absorption of these agents after subcutaneous injection is limited. Here, a mathematical framework to study the subcutaneous drug delivery of mAbs from injection to lymphatic uptake is presented. A three-dimensional poroelastic model is exploited to find the biomechanical response of the tissue by taking into account tissue deformation during the injection. The results show that including tissue deformability noticeably changes tissue poromechanical response due to the significant dependence of interstitial pressure on the tissue deformation. Moreover, the importance of the amount of lymph fluid at the injection site and the injection rate on the drug uptake to lymphatic capillaries is highlighted. Finally, variability of lymphatic uptake due to uncertainty in parameters including tissue poromechanical and lymphatic absorption parameters is evaluated. It is found that interstitial pressure due to injection is the major contributing factor in short-term lymphatic absorption, while the amount of lymph fluid at the site of injection determines the long-term absorption of the drug. Finally, it is shown that the lymphatic uptake results are consistent with experimental data available in the literature.
皮下注射因其患者舒适性和成本效益，已成为生物治疗药物可行的自我给药方式。然而，目前对于这些药物经皮下注射后的转运和吸收的了解有限。本文提出了一种数学框架，用于研究单克隆抗体经皮下给药后从注射到淋巴摄取的过程。利用一个三维多孔弹性模型，通过考虑注射过程中的组织变形，来寻找组织的生物力学响应。结果表明，由于间质压力对组织变形有显著的依赖性，因此包括组织可变形性在内，会显著改变组织的多孔力学响应。此外，还强调了注射部位的淋巴液量和注射速率对淋巴管摄取药物的重要性。最后，评估了由于包括组织多孔力学和淋巴吸收参数在内的参数不确定性导致的淋巴摄取变异性。结果表明，注射引起的间质压力是短期淋巴吸收的主要影响因素，而注射部位的淋巴液量决定了药物的长期吸收。最后，结果表明，淋巴摄取结果与文献中可用的实验数据一致。
