Vascular Targeting of Nano Carriers in Arterial Bifurcations

Cardiovascular diseases, including Atherosclerosis, are one of the leading causes of death in western society and there is a clinical need for new approaches for improved therapies. Targeted nano-therapeutics to atherosclerotic sites can provide safer, more efficient, and effective treatments through localization and release of encapsulated therapeutics specifically at the desired region. Studies have shown that atherosclerotic lesions localize at specific regions that may include tight curves and bifurcations along the blood vessel. Current approaches, including computational simulations, microfluidics, and animal models, fail to accurately model this multi-scale process in human arteries, where blood flow is dominant. The goal of our research is to understand particle dynamics, deposition, and adhesion of particles in models of arterial bifurcations under physiological conditions. We have designed and fabricated 3D real-sized arterial bifurcation models cultured with human endothelial cells and connected to a programmable perfusion system for injection of particles. Our results show that different particles tend to localize at specific sites within the bifurcation based on hemodynamics and particles properties. Moreover, we can conclude that particle targeting depends on several parameters such as (i) vessel geometry, (ii) blood flow and (iii) associated local hemodynamics. Therefore, engineering principles and methodologies may be valuable in developing nano-carriers for efficient targeted delivery [1].

[1] M. Khoury, M. Epshtein, H. Zidan, H. Zukerman, N. Korin, Mapping deposition of particles in reconstructed models of human arteries, J Control Release. 318 (2019) 78–85.