Heterogeneous blood flow in microvessels with applications to nanodrug transport and mass transfer into tumor tissue
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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.
KeywordsComputer simulation Cell-free layer Nanodrug delivery Extravasation
The use of ANSYS software (Canonsburg, PA) as part of the ANSYS-NCSU Professional Agreement is gratefully acknowledged.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Aarts PA, Van Den Broek SA, Prins GW, Kuiken GD, Sixma JJ, Heethaar RM (1988) Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. Arterioscler Thromb Vasc Biol 8(6):819–824Google Scholar
- Corley RA, Kabilan S, Kuprat AP, Carson JP, Jacob RE, Minard KR, Teeguarden JG, Timchalk C, Pipavath S, Glenny R, Einstein DR (2015) Comparative risks of aldehyde constituents in cigarette smoke using transient computational fluid dynamics/physiologically based pharmacokinetic models of the rat and human respiratory tracts. Toxic Sci 146:65–88CrossRefGoogle Scholar
- Kleinstreuer C (2015) Methods and Devices for Targeted Injection of Microspheres. U.S. Patent 9,149,605 issued 10/06/2015Google Scholar
- Kleinstreuer C, Xu Z (2018) Computational microfluidics applied to drug delivery in pulmonary and arterial systems. In: Song Y, Cheng D, Zhao L (eds) Microfluidics: fundamentals, devices, and applications. Wiley, WeinheimGoogle Scholar
- Mansour MH, Bressloff NW, Shearman CP (2010) Red blood cell migration in microvessels. Biorheology 47(1):73–93Google Scholar
- Olla P (1997) The lift on a tank-treading ellipsoidal cell in a shear flow. J Phys II 7(10):1533–1540Google Scholar