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Dissertation
Mechanism and efficacy of using polymeric nanoparticles for treating atherosclerosis
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2024
DOI:
https://doi.org/10.17918/00010859
Abstract
Atherosclerosis, a leading cause of cardiovascular disease, is characterized by the accumulation of lipid-laden macrophages (foam cells) in response to modified lipoproteins. As the disease progresses, advanced plaques can restrict or block blood flow, leading to severe cardiovascular complications such as heart attack and stroke. Despite the use of lipid-lowering and antiplatelet therapies, there remains a critical need for direct therapeutic strategies that can reduce plaques while simultaneously addressing the inflammatory and oxidative stress microenvironment. This study explores the potential of dextran sulfate-chitosan nanoparticles (DS-CH NPs) for the treatment of atherosclerosis. We demonstrate that these NPs promote cholesterol efflux from lipid-laden macrophages through the activation of multiple pathways, including ABCA1, SR-B1, and autophagy induction. Additionally, we show that apoA1 and apoE contribute to NP-mediated cholesterol efflux. By encapsulating curcumin within the NPs (CNPs), we enhanced their anti-inflammatory and antioxidant effects. In vivo experiments using an atherosclerotic mouse model confirmed that NPs specifically target atherosclerotic plaques, resulting in reduced plaque size, stabilized plaques, and decreased inflammation, oxidative stress, and hypertriglyceridemia. Safety assessments conducted both in vitro and in vivo have confirmed the safety of NPs and CNPs. These findings suggest that DS-CH NPs and CNPs have potential as novel therapies for atherosclerosis, addressing both cholesterol efflux and the underlying inflammatory and oxidative processes.
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Details
- Title
- Mechanism and efficacy of using polymeric nanoparticles for treating atherosclerosis
- Creators
- Yao Zhao
- Contributors
- Yinghui Zhong (Advisor)John Eberth (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xviii, 101 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991022019718204721