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Mathematical modeling of intraperitoneal drug delivery : simulation of drug distribution in a single tumor nodule

(2017) DRUG DELIVERY. 24(1). p.491-501
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Abstract
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.
Keywords
Drug transport, intraperitoneal chemotherapy, carcinomatosis, computational fluid dynamics, INTERSTITIAL FLUID PRESSURE, OVARIAN-CANCER, BRAIN-TUMORS, SOLID TUMORS, CHEMOTHERAPY, TRANSPORT, CISPLATIN, THERAPY, CARCINOMATOSIS, NORMALIZATION

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Chicago
Steuperaert, Margo, Giuseppe Falvo D’Urso Labate, Charlotte Debbaut, Olivier De Wever, Christian Vanhove, Wim Ceelen, and Patrick Segers. 2017. “Mathematical Modeling of Intraperitoneal Drug Delivery : Simulation of Drug Distribution in a Single Tumor Nodule.” Drug Delivery 24 (1): 491–501.
APA
Steuperaert, M., Falvo D’Urso Labate, G., Debbaut, C., De Wever, O., Vanhove, C., Ceelen, W., & Segers, P. (2017). Mathematical modeling of intraperitoneal drug delivery : simulation of drug distribution in a single tumor nodule. DRUG DELIVERY, 24(1), 491–501.
Vancouver
1.
Steuperaert M, Falvo D’Urso Labate G, Debbaut C, De Wever O, Vanhove C, Ceelen W, et al. Mathematical modeling of intraperitoneal drug delivery : simulation of drug distribution in a single tumor nodule. DRUG DELIVERY. 2017;24(1):491–501.
MLA
Steuperaert, Margo, Giuseppe Falvo D’Urso Labate, Charlotte Debbaut, et al. “Mathematical Modeling of Intraperitoneal Drug Delivery : Simulation of Drug Distribution in a Single Tumor Nodule.” DRUG DELIVERY 24.1 (2017): 491–501. Print.
@article{8509538,
  abstract     = {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.},
  author       = {Steuperaert, Margo and Falvo D'Urso Labate, Giuseppe and Debbaut, Charlotte and De Wever, Olivier and Vanhove, Christian and Ceelen, Wim and Segers, Patrick},
  issn         = {1071-7544},
  journal      = {DRUG DELIVERY},
  keyword      = {Drug transport,intraperitoneal chemotherapy,carcinomatosis,computational fluid dynamics,INTERSTITIAL FLUID PRESSURE,OVARIAN-CANCER,BRAIN-TUMORS,SOLID TUMORS,CHEMOTHERAPY,TRANSPORT,CISPLATIN,THERAPY,CARCINOMATOSIS,NORMALIZATION},
  language     = {eng},
  number       = {1},
  pages        = {491--501},
  title        = {Mathematical modeling of intraperitoneal drug delivery : simulation of drug distribution in a single tumor nodule},
  url          = {http://dx.doi.org/10.1080/10717544.2016.1269848},
  volume       = {24},
  year         = {2017},
}

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