Simulation of blood and oxygen distributions in a hepatic lobule with sinusoids obstructed by cancer cells.

The liver is one of the common metastatic sites for many cancers. The obstruction of sinusoids by circulating tumor cells changes liver microenvironments and is thus considered a source of hepatic metastases. To date, few studies provide detailed information, either experimentally or theoretically, concerning the changes in blood and oxygen distributions induced by the obstruction of sinusoids. In this study, we utilized a 3D porous medium-vascular tree geometric structure to mimic the hepatic lobule and studied theoretical blood flow and oxygen transport in the lobule. The simulation was validated with data from the literature. Then, the distributions of blood and oxygen in the presence of the obstruction by cancer cells were simulated. The area and degree of the liver damage induced by the obstruction were analyzed by comparing the difference of liver microenvironments between physiological (non-blocked sinusoid) and pathological (fully or partially blocked sinusoid) conditions and the minimum cancer cell sizes causing liver damage for various obstruction positions were obtained. The work presented in this study can be used to predict the degree of liver damage induced by the local ischemia caused by the obstruction of sinusoids and to characterize the relationship between hepatic metastases and liver microenvironments.

Simulation of the osmosis-based drug encapsulation in erythrocytes.

Drug-loaded erythrocytes have been proposed for the treatment of disease. A common way to load drugs into erythrocytes is to apply osmotic shock. Currently, osmosis-based drug encapsulation is studied mainly experimentally, whereas a related theoretical model is still incomplete. In this study, a set of equations is developed to simulate the osmosis-based drug-encapsulation process. First, the modeling is validated with hemolysis rates and the drug-loaded quantities to be found in the literature. Then, the variation of the erythrocyte volume, formation of the pore on the erythrocyte membrane, and quantities of drug loaded into and hemoglobin released from erythrocytes are studied. Finally, an optimized operating condition for encapsulating drugs is proposed. The results show that the volume of erythrocytes exposed to hypotonic NaCl solution increases first and then abruptly decreases because of the pore formation; afterwards, it again increases and then decreases slowly. In the presence of the pore, the drug is loaded by diffusion, whereas the leak-induced convection goes against the loading. For an allowed 45% hemolysis rate, with a 10% hematocrit, the optimized NaCl concentration is 0.44%, the optimized time for sealing the loaded erythrocytes with hypertonic NaCl solution is at 6.5 s, and the quantity of albumin (drug) loaded is 4.5 mg/ml cells.