Transport and deposition of nanoparticles in microvascular networks
Creators: name: Al-Siraj, Hassan M.
Publisher: name: No Publisher Supplied
Year: 2019

description: Targeted delivery of therapeutic drugs to specific sites in the body is becoming a norm for treating many diseases, such as cancer. Engineered nanoparticles have emerged as the most suitable carriers for this purpose. Often times, these particles are directly injected into the bloodstream and carried by the circulation to the targeted sites. The efficiency of the nanoparticle delivery depends on how many of them eventually reach the target sites before being removed by kidney filtration or by phagocytosis. Two hydrodynamic processes that are critical in the efficient delivery are margination of these particles from the core of a blood vessel towards the vessel wall, and adhesion of the particles on to the endothelial cell surface lining the vessel wall. Previous studies have considered margination and adhesion of nanoparticles in simple geometry, such as parallel plate flow chambers, and bifurcating channels. These studies have shown that the particle size and shape significantly affect their margination. However, blood vessels in the microcirculation form complex networks known as microvascular networks that are characterized by highly tortuous vessels, and frequent and hierarchical bifurcations and mergers. A detailed quantitative analysis of particle margination and adhesion under such complex geometry is missing. Towards that end, in this thesis we utilize a high-fidelity computational model of cellular-scale blood flow in physiologically-realistic microvascular networks to study the margination and adhesion of nano- and micro-particles. The objective is to understand the simultaneous effects of the flowing red blood cells and the complex geometry of the vasculatures on the margination and adhesion of particles. In the first part of the work, we model nanoparticles as volume-less point particles that are simply advected by the streamlines. We find that margination and adhesion are highly non-uniform across the networks. Specifically, we find that adhesion is significantly high in the bifurcation regions, while margination is high in the venular segments. In the second part of this work, we modeled particles as rigid finite-size spheres. Similar heterogeneity is observed herein, and the margination area density is also correlated to the CFL thickness. Arterioles and venules have high levels of margination and adhesion likelihood, while capillaries have the lowest. Our simulations show that irrespective of hematocrit levels and network topology, the accumulation of the marginated particles and the likelihood of adhesion increase with increasing particle size. In the last part of this work, we study shape effect of particles by considering oblate and prolate shapes. Similar heterogeneity is observed, and the margination area density is also correlated to the CFL thickness. Irrespective of hematocrit levels and network topology, margination of ellipsoidal particles was observed to be higher, with the oblate particles showing the maximum margination compared to other shapes. Our work underscores the importance of network topology on the distribution of the therapeutic drug within the targeted tissue.