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Antioxidant-Loaded Nanoparticles for...

Liao, Rick.

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Antioxidant-Loaded Nanoparticles for the Treatment of Excitotoxicity in Neurological Disease.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Antioxidant-Loaded Nanoparticles for the Treatment of Excitotoxicity in Neurological Disease./
作者:	Liao, Rick.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	130 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-04, Section: B.
Contained By:	Dissertations Abstracts International82-04B.
標題:	Chemical engineering. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28001866
ISBN:	9798684649363

Antioxidant-Loaded Nanoparticles for the Treatment of Excitotoxicity in Neurological Disease.
Liao, Rick.

Antioxidant-Loaded Nanoparticles for the Treatment of Excitotoxicity in Neurological Disease. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 130 p.

Source: Dissertations Abstracts International, Volume: 82-04, Section: B.

Thesis (Ph.D.)--University of Washington, 2020.

This item must not be sold to any third party vendors.

In the United States alone, neurological diseases affect tens of millions of people, costing $800 billion annually. In acute neurological injury, a process known as excitotoxicity manifests from energy failure or direct trauma, causing overexcitation of neurons that leads to neuronal toxicity. Following neuronal death, toxic metabolites and cellular debris accumulate in the brain, perpetuating excitotoxicity to neighboring neurons. Despite the heavy social and economic toll and extensive research into neurotherapeutic development, there are currently no approved therapeutics for targeting excitotoxicity after acute neurological injury. The difficulty in clinical translation is largely attributed to several barriers intrinsic to the brain, including traversing the blood-brain barrier (BBB) and diffusion through the brain parenchyma. Therefore, in addition to understanding the biological complexity of the brain, developing effective therapeutics is a drug delivery problem.To expedite the pre-clinical research process, we have developed a tailorable organotypic whole hemisphere (OWH) brain slice model, capable of mimicking in vivo processes including excitotoxity and neuroinflammation. Using OWH models, we can systematically study disease processes and screen therapeutics in a high-throughput fashion, bypassing delivery obstacles. To improve therapeutic enzyme delivery, we have developed brain-penetrating antioxidant enzyme-loaded polymeric nanoparticles that inhibit enzymatic degradation. Furthermore, via nanoparticle screening on the OWH model, we have elucidated the toxicity of a common polymeric nanoparticle formulation involving poly(ethylene glycol) (PEG) and sonication, and developed alternative biocompatible nanoparticle formulations. Finally, the OWH model has enabled detailed observation of disease-dependent nanoparticle-microglia interactions that can better inform drug delivery strategies. Throughout these studies, we have implemented a transdisciplinary approach that emphasizes thorough understanding of the neurobiology of disease and leverages chemical engineering fundamentals, to ultimately advance neurotherapeutic development.

ISBN: 9798684649363Subjects--Topical Terms:

560457
Chemical engineering.
Subjects--Index Terms:

Drug delivery

Antioxidant-Loaded Nanoparticles for the Treatment of Excitotoxicity in Neurological Disease.
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500 $a Advisor: Nance, Elizabeth.
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506 $a This item must not be sold to any third party vendors.
520 $a In the United States alone, neurological diseases affect tens of millions of people, costing $800 billion annually. In acute neurological injury, a process known as excitotoxicity manifests from energy failure or direct trauma, causing overexcitation of neurons that leads to neuronal toxicity. Following neuronal death, toxic metabolites and cellular debris accumulate in the brain, perpetuating excitotoxicity to neighboring neurons. Despite the heavy social and economic toll and extensive research into neurotherapeutic development, there are currently no approved therapeutics for targeting excitotoxicity after acute neurological injury. The difficulty in clinical translation is largely attributed to several barriers intrinsic to the brain, including traversing the blood-brain barrier (BBB) and diffusion through the brain parenchyma. Therefore, in addition to understanding the biological complexity of the brain, developing effective therapeutics is a drug delivery problem.To expedite the pre-clinical research process, we have developed a tailorable organotypic whole hemisphere (OWH) brain slice model, capable of mimicking in vivo processes including excitotoxity and neuroinflammation. Using OWH models, we can systematically study disease processes and screen therapeutics in a high-throughput fashion, bypassing delivery obstacles. To improve therapeutic enzyme delivery, we have developed brain-penetrating antioxidant enzyme-loaded polymeric nanoparticles that inhibit enzymatic degradation. Furthermore, via nanoparticle screening on the OWH model, we have elucidated the toxicity of a common polymeric nanoparticle formulation involving poly(ethylene glycol) (PEG) and sonication, and developed alternative biocompatible nanoparticle formulations. Finally, the OWH model has enabled detailed observation of disease-dependent nanoparticle-microglia interactions that can better inform drug delivery strategies. Throughout these studies, we have implemented a transdisciplinary approach that emphasizes thorough understanding of the neurobiology of disease and leverages chemical engineering fundamentals, to ultimately advance neurotherapeutic development.
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