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Title Exploring the Impact of Hemodynamic and Hemorheology in the Design of Carrier for Vascular-Targeted Drug Delivery in Atherosclerosis.
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Publication Date
Date Accessioned
Degree PhD
Discipline/Department Biomedical Engineering
Degree Level doctoral
University/Publisher University of Michigan
Abstract Recently, vascular targeting drug carriers (VTCs) have become one of the most distinguished aspects in pharmaceutical engineering.In order to sustain the ability of localized drug release over time, a carrier must survive through the circulation and be retained at a specific site.Therefore, a multitude of strategies have to be considered to achieve an optimal performing VTC design. Herein, the presented studies aim to elucidate the effect of VTC physical and material properties and the characteristics in prescribing the efficiency of VTCs to marginate to the vascular wall in atherosclerosis via in vitro flow assays and a mouse model atherosclerosis. In the first study, we explore the impact of VTC shapes on their functionality in targeting atherosclerosis and found that microrods were more effective at adhering to mouse aortas than micro and nanospheres, while nanorods particles displayed the same minimal levels as nanospheres due to poor localization to the vessel wall. We also found that targeted microparticles were retained at high levels in the lungs,likely due to molecular interaction with the pulmonary endothelium. In the second study, we explore how particle size, along with hemodynamics and hemorheology affect the adhesion of VTCs in a microfluidic assays. Microspheres were found to exhibit disproportionately higher vascular wall adhesion than nanospheres in all hemodynamic conditions, due to the higher ability to localize to the wall. Moreover, we also investigate the role of hemorheology(RBC’s dimension) in dictating the binding efficiency of spherical VTCs. Our results suggest that the ratio of RBCs size to the carrier size dictate the particle binding. Finally, we study the potential role of plasma proteins and material types which affect the adhesion of VTCs. The results show that the plasma proteins in different species have different effects on particle binding. This study offers the first evaluation of plasma proteins in different animal species to determine how they affect VTCs. In conclusion,we address the crucial factors of hemodynamics, hemorheology and plasma protein to VTC design. This important for many research fields, particularly in cardiovascular diseases as these parameters can be used to improve drug carrier performance.
Subjects/Keywords Vascular targeting drug delivery, Microparticles, Nanoparticles, Atherosclerosis; Biomedical Engineering; Engineering
Contributors Eniola-Adefeso, Lola (committee member); Pinsky, David (committee member); Takayama, Shuichi (committee member); Thurber, Greg Michael (committee member)
Language en
Rights Unrestricted
Country of Publication us
Record ID handle:2027.42/111579
Repository umich
Date Retrieved
Date Indexed 2019-03-07
Grantor University of Michigan, Horace H. Rackham School of Graduate Studies
Issued Date 2015-01-01 00:00:00
Note [thesisdegreename] PhD; [thesisdegreediscipline] Biomedical Engineering; [thesisdegreegrantor] University of Michigan, Horace H. Rackham School of Graduate Studies; [bitstreamurl] http://deepblue.lib.umich.edu/bitstream/2027.42/111579/1/katanamd_1.pdf;

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