Simulation of the delivery of doxorubicin to hepatoma

Purpose. To develop a two-dimensional simulation platform for the transport of doxorubicin to the hepatoma. To examine the temporal and spatial variat ion 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 volum e method to obtain the interstitial fluid pressure, velocity, and concentra tion 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 (similar to 1000 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 i s highest in the viable zone of the tumor at early times and in the necroti c core at later times, and lowest in the surrounding normal tissues. Diffus ion is the dominant form of transport for doxorubicin. Conclusions. Varying the volume of solution injected, while keeping the dos age the same, does not cause significant changes in the amount and distribu tion 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 zo nes. Cellular metabolism and DNA binding kinetics decrease the mean concent rations of drug by about 15 to 40%, as compared to the baseline case.