Effect of flow pulsatility and time-dependent release kinetics on stent-based delivery through atherosclerotic plaque

Abstract

The present work is concerned with an investigation of the effect of flow pulsatility and time-dependent release kinetics on the transport and retention of drug in a stent-based delivery through atherosclerotic plaque. Keeping the relevance of the physiological situation in view, an axi-symmetric two-dimensional model of drug delivery from a strut has been developed in cylindrical polar coordinate system. Here, the luminal drug transport is considered as an unsteady convection–diffusion process, while the drug transport within the arterial tissue is considered as a two-species model (both free and bound), capable of predicting the delivery of drug and its retention in the arterial tissue, in which the specific binding site action is modelled using a reversible chemical reaction. The transport of free drug is modelled as an unsteady convection–diffusion–reaction process, while the bound drug, assuming completely immobilised in the tissue, as an unsteady reaction process. An explicit finite-difference scheme in staggered grids has been developed to tackle numerically the governing equations of motion in order to compute the physiologically significant quantities with desired degree of accuracy. Model results predicted that, unlike within the tissue, the averaged free drug concentration increases with the increase of Re in the lumen and also the averaged concentrations of both drug forms decrease with increasing plaque thickness. Moreover, higher Peclet number in the tissue and coating results in lowering down the averaged concentrations of free as well as bound drug in the tissue and lumen. The present results predict that the presence of plaque dramatically affects the local pharmacokinetics and provides higher resistance to drug transfer in the arterial wall. The averaged concentration of free drug increases in the lumen due to flow pulsatility while a reverse trend is observed in the tissue. Additionally, modelling results also indicate that time-dependent release of drug in stent-based delivery diminishes the averaged concentration of both drug forms as compared to constant release kinetics. All the above observations are consistent with several existing results in the literature.