Device Integrity of Drug-eluting Depot Stent for Smart Drug Delivery

Abstract

Atherosclerosis, or hardening of the arteries, is a condition in which plaque, made of cholesterol, fatty substances, cellular waste products, calcium, and fi‐ brin, builds up inside the arteries. A metallic stent is a small mesh tube that is used to treat these narrowed arteries such as coronary artery diseases. The drug-eluting stent has a metallic stent platform coated with drug-polymer mix and has been shown to be superior to its metallic stent counterpart in reducing restenosis. In the past few years, a novel variation of the drug-eluting stent with micro-sized drug reservoirs (depot stent) has been introduced to the mar‐ ket. It allows smart programmable drug delivery with spatial/temporal control and has potential advantages over conventional stents. The drug-polymer mix compound can be altered from one reservoir to the next, allowing a highlycontrolled release of different medications. For example, this depot stent con‐ cept can be applied in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) si‐ multaneously. However, the creation of such drug reservoirs on the stent struts inevitably compromises its mechanical integrity. In this study, the effects of these drug reservoirs on stent key clinical attributes were systematically in‐ vestigated. We developed finite element models to predict the mechanical in‐ tegrity of a balloon-expandable stent at various stages of its function life such as manufacturing and acute deployment, as well as the stent radial strength and chronic fatigue life. Simulation results show that (1) creating drug reser‐ voirs on a stent strut could impact the stent fatigue resistance to certain de‐ grees; (2) drug reservoirs on the high stress concentration regions led to much greater loss in all key clinical attributes than reservoirs on other locations; (3) reservoir shape change resulted in little differences in all key clinical attributes; and (4) for the same drug loading capacity, larger and fewer reservoirs yielded © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. higher fatigue safety factor. These results can help future stent designers to achieve the optimal balance of stent mechanical integrity and smart drug de‐ livery, thereby opening up a wide variety of new opportunities for disease treatments. We also proposed an optimized depot stent with tripled drug ca‐ pacity and acceptable marginal trade-off in key clinical attributes when com‐ pared to the current drug-eluting stents. This depot stent prototype was manufactured for the demonstration of our design concept.