Mathematical Modeling of the Non-Steady State Diffusion of Antiproliferative Drugs from Coronary Artery Stents
Abstract – Coronary artery disease is the leading killer of people worldwide and results from clogging of the blood vessel with cholesterol-laden plaque. A mainstay of treatment for coronary artery disease is the drug-eluting stent, a metallic stent coated with polymer that releases therapeutic drugs into the arterial wall to prevent re-clotting. These drugs include the antiproliferative agents paclitaxel, sirolimus, everolimus, and zotarolimus. It is essential to ensure precise dosing of these agents; too little of a dose results in the stent being ineffective, but too much of a dose results in disastrous side effects including cell death and necrosis of the arterial wall. The objective of this study is to use the diffusion equation to model non-steady state diffusion of paclitaxel, sirolimus, everolimus, and zotarolimus from a drug-eluting stent through the arterial wall. The effects of molecular weight, diffusivity, time, and initial concentration on drug distribution were modeled. The model reveals that a high initial concentration of each drug is required to ensure adequate diffusion between stent struts and through the artery wall. These results can guide the design of drug-eluting stents as well as degradable drug-eluting stents and can predict the diffusion behavior of novel drugs for drug-eluting stents.