Modeling Dual Drug Delivery from Eluting Stents: The Influence of Non-Linear Binding Competition and Non-Uniform Drug Loading.

Abstract

There is increasing interest in simultaneous endovascular delivery of more than one drug from a drug-loaded stent into a diseased artery. There may be an opportunity to obtain a therapeutically desirable uptake profile of the two drugs over time by appropriate design of the initial drug distribution in the stent. Due to the non-linear, coupled nature of diffusion and reversible specific/non-specific binding of both drugs as well as competition between the drugs for a fixed binding site density, a comprehensive numerical investigation of this problem is critically needed. This paper presents numerical computation of dual drug delivery in a stent-artery system, accounting for diffusion as well as specific and non-specific reversible binding. The governing differential equations are discretized in space, followed by integration over time using a stiff numerical solver. Three different cases of initial dual drug distribution are considered. For the particular case of sirolimus and paclitaxel, results show that competition for a limited non-specific binding site density and the significant difference in the forward/backward reaction coefficients play a key role in determining the nature of drug uptake. The nature of initial distribution of the two drugs in the stent is also found to influence the binding process, which can potentially be used to engineer a desirable dual drug uptake profile. These results help improve the fundamental understanding of endovascular dual drug delivery. In addition, the numerical technique and results presented here may be helpful for designing and optimizing other drug delivery problems as well.