Thesis
The development of polysaccharide-based nanoparticles for the prevention of foam cell formation during atherosclerosis
Master of Science (M.S.), Drexel University
Jun 2014
DOI:
https://doi.org/10.17918/etd-7112
Abstract
Atherosclerosis is a complex, inflammatory disease that affects arteries and various cell types from the immune, circulatory, and metabolic systems. The progression of atherosclerosis can lead to coronary heart disease, one of the leading causes of death in developed nations. Some of the main factors that contribute to the progression of atherosclerosis are the oxidation of low-density lipoprotein (LDL), and the uptake of these oxidized products by macrophages within the intima of the blood vessels. The accumulation of oxidized LDL (oxLDL) within macrophages converts these cells into lipid-laden foam cells that contribute to the development of the atherosclerotic plaques. The death of accumulating foam cells within the atherosclerotic plaque leads to the formation of necrotic cores, which decrease the stability of the plaques, making them more thrombogenic. The resulting circulating thrombi can eventually cause myocardial infarction and death. Current methods of treatment for atherosclerosis, such as LDL apheresis and statin regimens, only makes the symptoms more manageable and do not treat the disease. Therefore, there is a need for a treatment of atherosclerosis that is able to target the mechanism which foam cells formation occurs, and inhibit this process. We propose a nanomedical approach for preventing the progression of atherosclerosis by inhibiting macrophage uptake of oxLDL. We have developed polysaccharide-based nanoparticles that can bind to class A macrophage scavenger receptors to inhibit uptake of oxLDL. The physical properties of these nanoparticles were optimized in order to prolong blood circulation time and increase colloidal stability of the particles. The optimized nanoparticles effectively inhibited the uptake of oxLDL by macrophages in dose-dependent and time-dependent manners, indicating the therapeutic potential of these nanoparticles.
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Details
- Title
- The development of polysaccharide-based nanoparticles for the prevention of foam cell formation during atherosclerosis
- Creators
- Kiran Ghandikota Murthy - DU
- Contributors
- Yinghui Zhong (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 73 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 7112; 991014632546204721