טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentKhoury Maria
SubjectVascular Targeting of Nano-Carriers in Atherosclerotic
Arterial Bifurcations
DepartmentDepartment of Biomedical Engineering
Supervisor Assistant Professor Netanel Korin
Full Thesis textFull thesis text - English Version


Abstract

Atherosclerosis is one of the leading causes of death in western society.  In spite of improvements in management of atherosclerosis and its associate complications, the incidence of the disease remains high and there is a need for new approaches of treatment. Nanomedicine, in particular targeted drug delivery, is a promising technology that can provide safer, more efficient and effective treatments through localized drug release. Atherosclerotic lesions localize at specific regions in the blood vessel, such as: tight curves and bifurcations, where a recirculation flow occurs and thus targeting drug carriers may be affected by the abnormal flow patterns at these sites. 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. Therefore, in this work, we aim to quantitatively study nano-carrier accumulation inside 3D reconstructed human arteries. We have designed and fabricated 3D real-sized arterial bifurcation models cultured with endothelial cells. The models were connected to a programmable perfusion system and particles were infused under physiological flow. Our results show that different particles tend to localize at specific sites within the bifurcation based on hemodynamics and particles properties. We demonstrate that vascular flow regions, associated with inflammation and plaque accumulation, e.g., recirculation flows, can be targeted using particles with different degrees of adhesiveness. Moreover, we show that pulsatile flow and red blood cells decrease the adhesion of the particles to the cells. In addition, our results reveal that in the case of inflamed cells, particles coated with specific ligands may alter the deposition map and provide selective adhesion of the particles inside the bifurcation model. Thus, we can conclude that particle targeting depends on several parameters such as (i) vessel geometry, (ii) blood flow and (iii) associated local hemodynamics. Moreover, engineering principles and methodologies may be valuable in developing nano-carriers for efficient targeted delivery.