Effects of through-hole drug reservoirs on key clinical attributes for drug-eluting depot stent.

摘要

Atherosclerosis, a condition related to cholesterol build-up and thickening of the inner wall of the artery, narrows or occludes the artery lumen. The drug-eluting stent is a major breakthrough for the treatment of such coronary artery diseases. In recent years, another innovative variation of the drug-eluting stent with drug reservoirs has been introduced. It allows programmable drug delivery with spatial and temporal control and has several potential advantages over traditional drug-eluting stents. However, creating such reservoirs on the stent struts may weaken the stent scaffolding and compromise its mechanical integrity. In this paper, the effects of these micro-sized through-hole drug reservoirs on several key clinically relevant functional attributes of the depot stent were investigated. Finite element models were developed to predict the mechanical integrity of a balloon-expandable stent at various stages such as manufacturing and deployment, as well as the stent radial strength and fatigue life. Results show that (1) creating drug reservoirs on a stent could impact the stent fatigue resistance to some degree; (2) drug reservoirs on the stent crowns 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; (4) for the same drug loading capacity, larger and fewer reservoirs yielded lower equivalent plastic strain and radial strength but higher fatigue safety factor; and (5) the proposed depot stent was proven to be a feasible design. Its total drug capacity could be tripled with acceptable marginal trade-off in key clinical attributes. These results can serve as the guidelines to help future stent designs to achieve the best combination of stent mechanical integrity and smart drug delivery in the future, thereby opening up a wide variety of new treatment potentials and opportunities.