Dissertation
Development and characterization of multifunctional nanoparticles for prevention and treatment of atherosclerosis
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2018
DOI:
https://doi.org/10.17918/00000106
Abstract
Atherosclerosis is the leading cause of cardiovascular disease, which can result in the development of myocardial infarctions, heart failure, strokes, and death. It is caused by signaling interactions between inflamed or dysfunctional endothelial, activated monocytes and lipid-laden macrophages (foam cells) in response to the accumulated modified lipoprotein within the vessel walls, and results in plaque development and chronic inflammation. Foam cells play a pivotal role in the occurrence and development of atherosclerosis by contributing to lipid accumulation, necrotic core expansion, plaque formation and further inflammatory amplification at the plaque sites. The management of atherosclerosis is challenged by high plasma concentration of circulating low-density lipoprotein (LDL) cholesterol, foam cell formation and inflammatory cascade. Current treatments tend to have very limited effect with several inherent drawbacks. In addition, they lack the ability to simultaneously address multiple mechanisms contributing to atherosclerosis. In this work, we harnessed nanotechnology to develop polymeric nanoparticles using dextran sulfate and chitosan. We found that these nanoparticles could bind to LDL and inhibit oxLDL internalization via scavenger receptor A and CD36. In addition, our study shows that they induced cholesterol efflux from foam cells possibly via the upregulation of Apolipoprotein A1 gene expression and acting as HDL particles to receive effluxed cholesterol. In vivo study using Apolipoprotein E -/- mouse model confirmed the safety of our nanoparticles, their ability to lower blood LDL cholesterol level without significantly effect on HDL level, and their efficacy in reducing atherosclerotic plaque size. Further, these nanoparticles can be loaded with curcumin, an anti-oxidative and anti-inflammatory drug. Our study shows that the curcumin-loaded nanoparticles can effectively inhibit foam cell formation and attenuate inflammation. Thus, this work highlights the promise of our nanoparticles to ameliorate or reverse the atherosclerosis progress.
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Details
- Title
- Development and characterization of multifunctional nanoparticles for prevention and treatment of atherosclerosis
- Creators
- Jia Nong
- Contributors
- Yinghui Zhong (Advisor)Kenneth A. Barbee (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xviii, 129 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991014695244204721