Flow-Mediated Drug Transport from Drug-Eluting Stents is Negligible: Numerical and In-vitro Investigations

  • Pujith R. S. Vijayaratnam
  • John A. Reizes
  • Tracie J. Barber


Prior numerical studies have shown that the blood flow patterns surrounding drug-eluting stents can enhance drug uptake in stented arteries. However, these studies employed steady-state simulations, wherein flow and drug transport parameters remained constant with respect to time. In the present study, numerical simulations and in-vitro experiments were performed to determine whether luminal blood flow patterns can truly enhance drug uptake in stented arteries. Unlike the aforementioned studies, the time-varying depletion of drug within the stent coating was modelled and the simulation results were validated qualitatively with the in-vitro experiments. The simulations showed that the non-Newtonian properties of blood, its complex near-wall behavior, and the pulsatility of its flow all affect drug uptake only modestly. Furthermore, flow-mediated drug transport was found to be negligible due to the rapid rate at which drug depletes at the stent coating surfaces that are exposed to arterial blood flow. For fluid dynamicists, these results show that steady-state simulations must be avoided when modelling drug transport in stented arteries. For device designers, these results may be used to optimize the shape of drug-eluting stent struts and coatings to improve stent efficacy.


Computational fluid dynamics Hemodynamics Blood rheology Drug delivery 



Area-weighted average concentration


Computational fluid dynamics





Pujith Vijayaratnam was supported by an Australian Postgraduate Award scholarship. This support did not otherwise influence the writing of this article. We would like to acknowledge Dr. Caroline O’Brien for developing the original in-vitro drug-eluting stent experiment and Yan Wang for helping to update the experiment for the current study. Finally, we would like to acknowledge Dr. Penny Martens, Dr. Justine Roberts, Dr. Josef Goding, and Dr. Khoon Lim for helping with the hydrogel preparation, and Dr. Vladimir Sytnyk and Dr. Ulises Aregueta Robles for their assistance with the microplate reader.


  1. 1.
    Aarts, P. A., S. A. van den Broek, G. W. Prins, G. D. Kuiken, J. J. Sixma, and R. M. Heethaar. Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. Arterioscler. Thromb. Vasc. Biol. 8:819–824, 1988.Google Scholar
  2. 2.
    Balakrishnan, B., J. F. Dooley, G. Kopia, and E. R. Edelman. Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. J. Controlled Release. 123:100–108, 2007.CrossRefGoogle Scholar
  3. 3.
    Balakrishnan, B., A. R. Tzafriri, P. Seifert, A. Groothuis, C. Rogers, and E. R. Edelman. Strut position, blood flow, and drug deposition. Circulation. 111:2958–2965, 2005.CrossRefGoogle Scholar
  4. 4.
    Ballyk, P. D., D. A. Steinman, and C. R. Ethier. Simulation of non-Newtonian blood flow in an end-to-side anastomosis. Biorheology. 31:565–586, 1994.CrossRefGoogle Scholar
  5. 5.
    Bryant, S. J., K. A. Davis-Arehart, N. Luo, R. K. Shoemaker, J. A. Arthur, and K. S. Anseth. Synthesis and characterization of photopolymerized multifunctional hydrogels: water-soluble poly (vinyl alcohol) and chondroitin sulfate macromers for chondrocyte encapsulation. Macromolecules. 37:6726–6733, 2004.CrossRefGoogle Scholar
  6. 6.
    Chen, Y., Y. Xiong, W. Jiang, F. Yan, M. Guo, Q. Wang, and Y. Fan. Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution. Biomed. Eng. Online. 14:S16, 2015.CrossRefGoogle Scholar
  7. 7.
    Cheng, N. S. Formula for the viscosity of a glycerol–water mixture. Ind. Eng. Chem. Res. 47:3285–3288, 2008.CrossRefGoogle Scholar
  8. 8.
    Cho, Y. I., and K. R. Kensey. Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows. Biorheology. 28:241–262, 1991.CrossRefGoogle Scholar
  9. 9.
    Colombo, A., J. Drzewiecki, A. Banning, E. Grube, K. Hauptmann, S. Silber, D. Dudek, S. Fort, F. Schiele, K. Zmudka, and G. Guagliumi. Randomized study to assess the effectiveness of slow-and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation. 108:788–794, 2003.CrossRefGoogle Scholar
  10. 10.
    Creel, C. J., M. A. Lovich, and E. R. Edelman. Arterial paclitaxel distribution and deposition. Circ. Res. 86:879–884, 2000.CrossRefGoogle Scholar
  11. 11.
    Cutrì, E., P. Zunino, S. Morlacchi, C. Chiastra, and F. Migliavacca. Drug delivery patterns for different stenting techniques in coronary bifurcations: a comparative computational study. Biomech. Model Mechanobiol. 12:657–669, 2013.CrossRefGoogle Scholar
  12. 12.
    D’Angelo, C., P. Zunino, A. Porpora, S. Morlacchi, and F. Migliavacca. Model reduction strategies enable computational analysis of controlled drug release from cardiovascular stents. SIAM J. Appl. Math. 71:2312–2333, 2011.CrossRefGoogle Scholar
  13. 13.
    Deen, W. M. Analysis of Transport Phenomena, Topics in Chemical Engineering. Oxford: University Press, 1998.Google Scholar
  14. 14.
    Henry, F. S. Flow in stented arteries. In: Intra and Extra Corporeal Cardiovascular Fluid Dynamics, edited by P. Vendonck, and K. Perktold. Southampton: WIT Press, 2000.Google Scholar
  15. 15.
    Higuchi, T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52:1145–1149, 1963.CrossRefGoogle Scholar
  16. 16.
    Hwang, C. W., D. Wu, and E. R. Edelman. Impact of transport and drug properties on the local pharmacology of drug-eluting stents. Int. J. Cardiovasc. Intervent. 5:7–12, 2003.CrossRefGoogle Scholar
  17. 17.
    Kolachalama, V. B., E. G. Levine, and E. R. Edelman. Luminal flow amplifies stent-based drug deposition in arterial bifurcations. PLoS ONE 4:e8105, 2009.CrossRefGoogle Scholar
  18. 18.
    Kolachalama, V. B., A. R. Tzafriri, D. Y. Arifin, and E. R. Edelman. Luminal flow patterns dictate arterial drug deposition in stent-based delivery. J. Controlled Release. 133:24–30, 2009.CrossRefGoogle Scholar
  19. 19.
    Lovich, M. A., C. Creel, K. Hong, C. W. Hwang, and E. R. Edelman. Carrier proteins determine local pharmacokinetics and arterial distribution of paclitaxel. J. Pharm. Sci. 90:1324–1335, 2001.CrossRefGoogle Scholar
  20. 20.
    Martin, K., and R. Mehran. Role of coronary drug-eluting stents in current clinical practice. Lung Cancer 15:05, 2018.Google Scholar
  21. 21.
    Migliavacca, F., F. Gervaso, M. Prosi, P. Zunino, S. Minisini, L. Formaggia, and G. Dubini. Expansion and drug elution model of a coronary stent. Comput. Methods Biomech. Biomed. Eng. 10:63–73, 2007.CrossRefGoogle Scholar
  22. 22.
    O’Brien, C. C., C. H. Finch, T. J. Barber, P. Martens, and A. Simmons. Analysis of drug distribution from a simulated drug-eluting stent strut using an in vitro framework. Ann. Biomed. Eng. 40:2687–2696, 2012.CrossRefGoogle Scholar
  23. 23.
    O’Brien, C. C., V. B. Kolachalama, T. J. Barber, A. Simmons, and E. R. Edelman. Impact of flow pulsatility on arterial drug distribution in stent-based therapy. J. Controll. Release. 168:115–124, 2013.CrossRefGoogle Scholar
  24. 24.
    Pedersen, L., E. B. Nielsen, M. K. Christensen, M. Buchwald, and M. Nybo. Measurement of plasma viscosity by free oscillation rheometry: imprecision, sample stability and establishment of a new reference range. Ann. Clin. Biochem. 51:495–498, 2014.CrossRefGoogle Scholar
  25. 25.
    Rikhtegar, F., E. R. Edelman, U. Olgac, D. Poulikakos, and V. Kurtcuoglu. Drug deposition in coronary arteries with overlapping drug-eluting stents. J. Controll. Release. 238:1–9, 2016.CrossRefGoogle Scholar
  26. 26.
    Roache, P. J. Quantification of uncertainty in computational fluid dynamics. Annu. Rev. Fluid Mech. 29:123–160, 1997.CrossRefGoogle Scholar
  27. 27.
    Saltzman, W. M. Drug Delivery: Engineering Principles for Drug Therapy. Oxford: Oxford University Press, 2001.Google Scholar
  28. 28.
    Taylor, C. A., T. J. Hughes, and C. K. Zarins. Finite element modeling of three-dimensional pulsatile flow in the abdominal aorta: relevance to atherosclerosis. Ann. Biomed. Eng. 26:975–987, 1998.CrossRefGoogle Scholar
  29. 29.
    Vijayaratnam, P. R. S., T. J. Barber, and J. A. Reizes. The localized hemodynamics of drug-eluting stents are not improved by the presence of magnetic struts. J. Biomech. Eng. 139:014502, 2017.CrossRefGoogle Scholar
  30. 30.
    Vijayaratnam, P. R., C. C. O’Brien, J. A. Reizes, T. J. Barber, and E. R. Edelman. The impact of blood rheology on drug transport in stented arteries: Steady simulations. PLoS ONE. 10:e0128178, 2015.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2018

Authors and Affiliations

  • Pujith R. S. Vijayaratnam
    • 1
  • John A. Reizes
    • 1
  • Tracie J. Barber
    • 1
  1. 1.UNSW SydneySydneyAustralia

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