Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule.
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.
a Biofluid, Tissue and Solid Mechanics for Medical Applications (bioMMeda), Department of Electronics and Information Systems, iMinds Medical IT Department, Ghent University , Ghent , Belgium.
Margo
M
Steuperaert
b Department of Environmental and Chemical Engineering , University of Calabria , Rende , CS , Italy.
Giuseppe
G
Falvo D'Urso Labate
a Biofluid, Tissue and Solid Mechanics for Medical Applications (bioMMeda), Department of Electronics and Information Systems, iMinds Medical IT Department, Ghent University , Ghent , Belgium.
Charlotte
C
Debbaut
c Department of Radiation Oncology and Experimental Cancer Research.
Olivier
O
De Wever
d Infinity (iMinds-IBiTech-MEDISIP), Department of Electronics and Information Systems , and.
Christian
C
Vanhove
e Department of Surgery, Cancer Research Institute Ghent (CRIG), Ghent University , Ghent , Belgium.
Wim
W
Ceelen
a Biofluid, Tissue and Solid Mechanics for Medical Applications (bioMMeda), Department of Electronics and Information Systems, iMinds Medical IT Department, Ghent University , Ghent , Belgium.
Patrick
P
Segers
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003198:Computer Simulation; D004058:Diffusion; D006801:Humans; D057446:Hydrodynamics; D007274:Injections, Intraperitoneal; D008954:Models, Biological; D009336:Necrosis; D009716:Numerical Analysis, Computer-Assisted; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D010539:Permeability; D014018:Tissue Distribution; D047368:Tumor Burden
D000970:Antineoplastic Agents
Drug transport; carcinomatosis; computational fluid dynamics; intraperitoneal chemotherapy