Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls

Abstract

A vast majority of heart attacks occur due to rapid progression of plaque buildup in the coronary arteries that supply blood to the heart muscles. The diseased arteries can be treated with drugs delivered locally to vulnerable plaques—ones that may rupture and release emboli, resulting in the formation of thrombus, or blood clot that can cause blockage of the arterial lumen. In designing these local drug delivery devices, important issues regarding drug distribution and targeting need to be addressed to ensure device design optimization as physiological forces can cause the local concentration to be very different from mean drug tissue concentration estimated from in vitro experiments and animal studies. Therefore, the main objective of this work was to develop a computational tool-set to support the design of a catheter-based local drug delivery system that uses nanoparticles as drug carriers by simulating drug transport and quantifying local drug distribution in coronary artery walls. Toward this end, a three dimensional mathematical model of coupled transport of drug and drug-encapsulated nanoparticles was developed and solved numerically by applying finite element based isogeometric analysis that uses NURBS-based techniques to describe the artery wall geometry. To gain insight into the parametric sensitivity of drug distribution, a study of the effect of Damkohler number and Peclet number was carried out. The tool was then applied to a three-dimensional idealized multilayered model of the coronary artery wall under healthy and diseased condition. Preliminary results indicated that use of realistic geometry is essential in creating physiological flow features and transport forces necessary for developing catheter-based drug delivery design procedures. Hence, simulations were run on a patient-specific coronary artery wall segment with a typical atherosclerotic plaque characterized by a lipid pool encased by a thin fibrous cap. Results show that plaque heterogeneity and artery wall inhomogeneity have a considerable effect on drug distribution. The computational tool-set developed was able to successfully capture trends observed in local drug delivery by incorporating a multitude of relevant physiological phenomena, and thus demonstrated its potential utility in optimizing drug design parameters including delivery location, nanoparticle surface properties and drug release rate.