Steuperaert Margo, Falvo D'Urso Labate Giuseppe, Debbaut Charlotte, De Wever Olivier, Vanhove Christian, Ceelen Wim, Segers Patrick
a Biofluid, Tissue and Solid Mechanics for Medical Applications (bioMMeda), Department of Electronics and Information Systems, iMinds Medical IT Department, Ghent University , Ghent , Belgium.
b Department of Environmental and Chemical Engineering , University of Calabria , Rende , CS , Italy.
Drug Deliv. 2017 Nov;24(1):491-501. doi: 10.1080/10717544.2016.1269848.
The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy. Overall, smaller tumors showed better penetration than larger ones, which could be attributed to the lower IFP in smaller tumors. Furthermore, the model demonstrated large improvements in penetration depth by subjecting the tumor nodules to vascular normalization therapy, and illustrated the importance of the drug that is used for therapy. Explicitly modeling the necrotic core had a limited effect on the simulated penetration. Similarly, the penetration depth remained virtually constant when the Darcy permeability of the tissue changed. Our findings illustrate that the developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy.
腹腔内（IP）化疗是腹膜癌病的一种替代治疗方法，与静脉给药相比，它能使肿瘤内细胞毒性药物的浓度更高。然而，药物渗透深度仍局限于几毫米。因此，有必要更好地了解这种低渗透背后的限制因素，以改善腹腔内化疗给药。通过建立一个用于肿瘤结节内药物渗透的三维计算流体动力学（CFD）模型，我们研究了腹腔内化疗期间一些关键参数对药物传输和渗透深度的影响。总体而言，较小的肿瘤比较大的肿瘤显示出更好的渗透效果，这可能归因于较小肿瘤中较低的间质流体压力（IFP）。此外，该模型表明，对肿瘤结节进行血管正常化治疗可大幅提高渗透深度，并说明了用于治疗的药物的重要性。明确模拟坏死核心对模拟渗透的影响有限。同样，当组织的达西渗透率改变时，渗透深度实际上保持不变。我们的研究结果表明，所开发的参数化CFD模型是一个强大的工具，能更深入了解腹腔内化疗期间的药物传输和渗透情况。
