Shear Stess-Induced Nanoparticle Drug Delivery in the Right Coronary Artery
Allan-Rahill, Nash; Iruvanti, Sushruta; Miller, Nick; Sarubbe, Jerry
Shear stress-sensitive nanoparticles are a promising new field for drug delivery. This novel method may allow the targeted release of drugs such as statins or vasodilators to areas of high shear in the bloodstream, as occurs near a stenosis. Previous work claims that shear stress-sensitive nanoparticles may deliver a targeted release of clot-busting or cholesterol-fighting drugs to arterial plaque . However, these studies have only examined flow characteristics near plaques and have not considered the movement of nanoparticles within these flows or the complex process of drug diffusion from the particle's shear location into the plaque. The study outlined here considers the entire process from nanoparticle entry upstream of the plaque through drug diffusion into the tissue. A right coronary artery with a Type I plaque morphology was designed using the 3D CAD design software SolidWorks®. COMSOL Multiphysics®, a commercially available modeling software, was used to model blood flow past this plaque with a varying inlet velocity to simulate pulsatile flow. Particle diffusion through the blood and subsequent drug diffusion into the tissue were simulated. Average dimensional values and flow velocities for men were used since they are more at risk for developing atherosclerosis. The results of these simulations showed that the plaque buildup at 35% stenosis causes sufficient shear stress to break the nanoparticles, releasing the drug into the blood. Most drug, once it was released from the nanoparticles, was found to diffuse into the downstream half of the plaque. Moreover, it was found that the optimal breaking shear stress of the nanoparticles for targeted drug delivery to the stenosis was nearly the maximum shear stress achieved in the flow at 75 Pa, while the optimal infusion concentration is close to the maximum clinically allowable at 0.045 mol/m3 . This computational study has filled an important void in the body of research on this novel drug delivery method. It has verified the rupture of nanoparticles under 35% stenotic conditions while showing subsequent drug diffusion patterns, which suggests that this method may not be suited for targeting drug delivery to arterial plaques. Further research should examine the effects of arterial wall compliance, consider non-Newtonian blood flow, and test realistic plaque geometries obtained, for example, via intravascular ultrasound (IVUS). Though shear stress-sensitive nanoparticle drug delivery may not ideally target drug to arterial stenoses, this novel method may prove useful for modeling tumorigenic systems, where fluid shear stress has been shown to affect cancer cell motility.
Atherosclerosis, Plaque, Nanoparticles, Coronary Artery Disease, Shear Stress