(639d) Particle Size Dictates the Efficacy of Vascular-Targeted Drug Carriers in Disturbed Flow Relevant in Atherosclerosis

Vascular-targeted drug delivery is a promising approach for the treatment of atherosclerosis due to the vast involvement of endothelium in the initiation and growth of plaque, which is characteristic of atherosclerosis. Plaque preferentially develops at the bifurcation of coronary blood vessels where disturbed flow and streamline separation occurs. Disturbed flow includes pulsatile flow, regulated by the cardiac cycle, and recirculation flow, which occurs in areas with sudden flow expansion in the arterial tree. Existing literature has focused on understanding the mechanism of blood cell recruitment to inflamed endothelium in disturbed flow relative to atherogenesis. Absent in the literature, are work focused on the ability of vascular-targeted drug carriers to interact with the vessel wall in disturbed flow ? an important consideration that will control the effectiveness of targeted therapy. Though nano-sized spherical particles are widely proposed for use in vascular-targeted drug delivery, little evidence has been presented in the literature as to their optimal use. Here, we report the role of particle size along with human blood flow dynamics on the efficiency of drug carrier interaction with inflamed endothelium both in vitro and in vivo in mice. Our results suggest that particle binding efficiency in disturbed (pulsatile and recirculating) flow increases as spherical diameter increased from 100 nm to 5 μm. We also find that recirculation in flow redistributes particle localization to the wall proximity, which increases the opportunity of particle binding far downstream. Overall, the presented data suggests that micron-sized spherical particles, not nanoparticles, are optimal for vascular-targeted drug delivery applications in medium to large vessel relevant in atherosclerosis and other cardiovascular diseases.