A Two-Species Drug Delivery Model is Required to Predict Deposition from Drug-Eluting Stents

Abstract

Drug-eluting stents are the treatment of choice for reducing restenosis rates after plaque removal. The drugs in use today partition between the plasma phase and binding sites in the vessel wall, where preferential binding leads to buildup and an increase in tissue residence times. Computational modeling has been used extensively to reveal key relationships between geometry, flow, drug physicochemical properties and the resulting deposition patterns. Yet, in spite of its’ simplicity, very little work has been done to include the presence of two drug forms in the modeling framework. Therefore, this paper outlines a method for simulating the transport of bound and unbound drug in a vessel wall. The method is demonstrated with a three-dimensional model of a standard stainless steel stent of Palmaz design deployed in a coronary artery. Drug transport in the vessel wall is driven by both diffusion and convection. The drug transport model also includes a reversible equilibrium reaction to account for tissue binding. The relative reaction rates control the interconversion of drug between the bound and unbound states. Results include a parametric study of convection–diffusion and equilibrium coefficient, providing an understanding of how drug physicochemical properties affect retention and distribution in the tissue. They also provide a first look at the relative distribution of the two drug forms in a full three-dimensional model of the vessel wall. The model also reveals how a single species drug delivery model can not accurately predict the distribution of bound drug. We therefore conclude that a two-species approach that includes reversible binding is the way forward for future stent-based drug delivery simulations.