Y M Goh1, H L Kong, C H Wang. 1. Department of Chemical and Environmental Engineering National University of Singapore.
Abstract
PURPOSE: To develop a two-dimensional simulation platform for the transport of doxorubicin to the hepatoma. To examine the temporal and spatial variation of doxorubicin concentration and its penetration into the tumor and the surrounding normal tissues. METHODS: Simulations are carried out with Fluent/UNS using the finite volume method to obtain the interstitial fluid pressure, velocity, and concentration profiles. RESULTS: Interstitial fluid pressure in the tumor and core reaches a steady state value in about 800 s, corresponding well with the assumed time scale for interstitial matrix fluid percolation (-1,000 s). There is a strong correlation between the drug concentration in the interstitial space of tumor and blood plasma for time >> 1 h. Concentration of doxorubicin is highest in the viable zone of the tumor at early times and in the necrotic core at later times, and lowest in the surrounding normal tissues. Diffusion is the dominant form of transport for doxorubicin. CONCLUSIONS: Varying the volume of solution injected, while keeping the dosage the same, does not cause significant changes in the amount and distribution of drug in the tumor. A higher vascular exchange area leads to higher concentrations of drug in the tumor. Lymphatic drainage in the tumor causes negligible reductions in the mean concentrations in all three different zones. Cellular metabolism and DNA binding kinetics decrease the mean concentrations of drug by about 15 to 40%, as compared to the baseline case.
PURPOSE: To develop a two-dimensional simulation platform for the transport of doxorubicin to the hepatoma. To examine the temporal and spatial variation of doxorubicin concentration and its penetration into the tumor and the surrounding normal tissues. METHODS: Simulations are carried out with Fluent/UNS using the finite volume method to obtain the interstitial fluid pressure, velocity, and concentration profiles. RESULTS: Interstitial fluid pressure in the tumor and core reaches a steady state value in about 800 s, corresponding well with the assumed time scale for interstitial matrix fluid percolation (-1,000 s). There is a strong correlation between the drug concentration in the interstitial space of tumor and blood plasma for time >> 1 h. Concentration of doxorubicin is highest in the viable zone of the tumor at early times and in the necrotic core at later times, and lowest in the surrounding normal tissues. Diffusion is the dominant form of transport for doxorubicin. CONCLUSIONS: Varying the volume of solution injected, while keeping the dosage the same, does not cause significant changes in the amount and distribution of drug in the tumor. A higher vascular exchange area leads to higher concentrations of drug in the tumor. Lymphatic drainage in the tumor causes negligible reductions in the mean concentrations in all three different zones. Cellular metabolism and DNA binding kinetics decrease the mean concentrations of drug by about 15 to 40%, as compared to the baseline case.
Authors: Margo Steuperaert; Giuseppe Falvo D'Urso Labate; Charlotte Debbaut; Olivier De Wever; Christian Vanhove; Wim Ceelen; Patrick Segers Journal: Drug Deliv Date: 2017-11 Impact factor: 6.419