The Role of Hemodynamics in Determining Drug Deposition in Stent-Based Delivery

Abstract

Drug-eluting stents are used routinely in coronary arteries, and are increasingly being considered for non-coronary vascular beds. Yet, mechanisms governing the efficacy of the drug-eluting stent are still being understood, in particular those physiologic and device related factors that determine the arterial distribution of therapeutic agents. The primary aim of this thesis is to determine the role of vascular-bed dependent luminal flow in dictating the extent of arterial drug deposition from endovascular stents. An integrated framework comprising computational and bench-top models has been formulated to explore the relative contributions of key hemodynamic parameters intrinsic to a vascular bed. Using a novel, dynamically similar bench-top model, we determine that arterial drug patterns are sensitive to the net luminal flow environment, created by mean flow rate and strut geometry. This analysis is then extended to consider the mechanisms that govern the pulsatile nature of blood flow, and how they modulate arterial drug distribution. A coupled framework comprising a computational fluid dynamics and mass transfer model, along with the custom-designed bench-top model allowed us to investigate scenarios that are not possible with animal models alone. Model-based simulations predicted that when stent struts were fully-apposed only the time-averaged blood flow through the lumen (or the mean blood flow rate defined by Reynolds number) dictated the pattern of drug distribution, and not the factors that quantify the unsteady nature of blood. Contrastingly, when struts were malapposed from the wall, arterial drug uptake was found to be directly dependent on the unsteady flow effects. Finally the effects of geometry-induced changes to the core flow were investigated, with focus on stent position at the aorta-renal ostia. The results showed that further to those local flow alterations induced by the stent strut, tissue drug uptake at the aorta-renal ostia is also modulated by both relative stent position with respect to the ostia and changes to the core flow due to bifurcation and curvature at the ostia.