Heterogeneous blood flow in microvessels with applications to nanodrug transport and mass transfer into tumor tissue.

Nanodrug transport in tumor microvasculature and deposition/extravasation into tumor tissue are an important link in the nanodrug delivery process. Considering heterogeneous blood flow, such a dual process is numerically studied. The hematocrit distribution is solved by directly considering the forces experienced by the red blood cells (RBCs), i.e., the wall lift force and the random cell collision force. Using a straight microvessel as a test bed, validated computer simulations are performed to determine blood flow characteristics as well as the resulting nanodrug distribution and extravasation. The results confirm that RBCs migrate away from the vessel wall, leaving a cell-free layer (CFL). Nanodrug particles tend to preferentially accumulate in the CFL, leading to increased concentration near the endothelial surface layer. However, shear-induced NP diffusion is diminished within the CFL, causing to a much slower lateral transport rate into tumor tissue. These competing effects determine the NP deposition/extravasation rates. The present modeling framework and NP flux results provide new physical insight. The analysis can be readily extended to simulations of NP transport in blood microvessels of actual tumors.