Modeling the transport of drugs eluted from stents: physical phenomena driving drug distribution in the arterial wall

Abstract

Despite recent data that suggest that the overall performance of drug-eluting stents (DES) is superior to that of bare-metal stents, the long-term safety and efficacy of DES remain controversial. The risk of late stent thrombosis associated with the use of DES has also motivated the development of a new and promising treatment option in recent years, namely drug-coated balloons (DCB). Contrary to DES where the drug of choice is typically sirolimus and its derivatives, DCB use paclitaxel since the use of sirolimus does not appear to lead to satisfactory results. Since both sirolimus and paclitaxel are highly lipophilic drugs with similar transport properties, the reason for the success of paclitaxel but not sirolimus in DCB remains unclear. Computational models of the transport of drugs eluted from DES or DCB within the arterial wall promise to enhance our understanding of the performance of these devices. The present study develops a computational model of the transport of the two drugs paclitaxel and sirolimus eluted from DES in the arterial wall. The model takes into account the multilayered structure of the arterial wall and incorporates a reversible binding model to describe drug interactions with the constituents of the arterial wall. The present results demonstrate that the transport of paclitaxel in the arterial wall is dominated by convection while the transport of sirolimus is dominated by the binding process. These marked differences suggest that drug release kinetics of DES should be tailored to the type of drug used.