Computational Analysis to Study the Efficiency of Shear-Activated Nano-Therapeutics in the Treatment of Atherosclerosis

Strokes are the fifth leading cause of death in the United States and can cause long-term disabilities in patients who survive a stroke. The vast majority of these strokes are ischemic, primarily caused by intracranial atherosclerosis. Most therapies to combat intracranial atherosclerosis simply manage it and do not remove the buildup of plaque. Targeted shear-activated nano-therapeutics are currently being developed to remove these plaques. We discuss the roles that aggregate particle density, aggregate particle diameter, vessel geometry, stenosis shape, and breakup threshold play in the efficiency of this new technology. Computational studies were performed to test these parameters in three idealized vessels with varying curvatures (straight, quarter-circle, semi-circle) and two different stenosis shapes (concentric, eccentric). We find that curvature plays a large role in the breakup threshold. The optimal breakup threshold for a semi-circular shaped vessel is 4.5 times that of a straight vessel, yet the less curved quarter-circle shaped vessel has an optimal breakup threshold that is 6.3 times that of the straight vessel. Therefore, no quantifiable pattern was discovered between geometry curvature and optimal threshold value. Curvature also plays a large role in how particle diameter affects the efficiency of these nano-therapeutics. Although the effects of particle size between 1 and 5 μm is minimal, the optimal particle diameter for a straight vessel was located at the smallest end of the tested range while the optimal diameter for the curved case was located at the largest end of the tested range. Particle-specific density was explored and found to have a negligible effect. Finally, curvature and stenosis location (superior, inferior, and ventral/dorsal) play a large role in optimizing breakup position. It is optimal for the stenosis to be in the path of the aggregate particle.