Chapters authored
Device Integrity of Drug-eluting Depot Stent for Smart Drug Delivery
Atherosclerosis, or hardening of the arteries, is a condition in which plaque, made of cholesterol, fatty substances, cellular waste products, calcium, and fibrin, 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 market. 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 highly-controlled release of different medications. For example, this depot stent concept can be applied in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) simultaneously. 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 investigated. We developed finite element models to predict the mechanical integrity 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 reservoirs on a stent strut could impact the stent fatigue resistance to certain degrees; (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 higher fatigue safety factor. These results can help future stent designers to achieve the optimal balance of stent mechanical integrity and smart drug delivery, thereby opening up a wide variety of new opportunities for disease treatments. We also proposed an optimized depot stent with tripled drug capacity and acceptable marginal trade-off in key clinical attributes when compared to the current drug-eluting stents. This depot stent prototype was manufactured for the demonstration of our design concept.
Part of the book: Smart Drug Delivery System