Effect of Atherosclerotic Plaque on Drug Delivery from Drug-eluting Stent

Abstract

Atherosclerotic plaque formation due to lipid accumulation in the arterial wall is the major cause of stenotic coronary disease. To restore distal coronary blood supply and overcome restenotic events presented by bare wire stents, drug-eluting stent (DES) implantation is now commonly used to treat stenotic coronary disease. However, while its long-term outcome is still unavailable, early clinical results appear to be inconsistent. The use of computational models is believed to be important in understanding DES and to elucidate the delivery of drug and improve the efficacy of DES. The presence of plaque in the stented region is expected to affect drug pharmacokinetics related to DES. In this study, a 2-dimensional model which drug transfer was coupled with both luminal and transmural flows was presented to investigate drug deposition and distribution in the arterial wall. Paclitaxel was used as a model drug and its interaction with the binding sites in the tissue was treated as a reversible binding process. As predicted, the presence of plaque dramatically affects the local pharmacokinetics. Thick plaque absorbs more drugs and provides higher resistance to drug transfer in the arterial wall compared to thin plaque. Study on the effect of drug diffusivity in the plaque on drug deposition reveals that higher diffusion coefficient results in lower drug content in the arterial wall. Meanwhile, when drug partition coefficient in the plaque was varied within the range for paclitaxel, it showed negligible effect on drug deposition. In conclusion, the presence and property of plaque have an effect on the delivery of drugs in arterial wall and should be included in the modeling of drug delivery from a DES to improve the design of stent to achieve the best therapeutic outcome.