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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林?輝(Feng-Huei Lin) | |
dc.contributor.author | Ching-Yun Yang | en |
dc.contributor.author | 楊景昀 | zh_TW |
dc.date.accessioned | 2021-06-17T07:06:15Z | - |
dc.date.available | 2020-08-05 | |
dc.date.copyright | 2019-08-05 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-07-25 | |
dc.identifier.citation | 參考文獻
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72789 | - |
dc.description.abstract | 根據2015年阿茲海默症期刊指出每三秒就有一位失智症患者產生,並預估在2050年時世界失智症總人口將來到一億三千萬人,其背後醫療支出也將達到10兆美金,已成為現今老年化社會無法忽視的問題。而失智症有六成至八成是源自於阿茲海默症,阿茲海默症在現今治療中仍有許多瓶頸需要突破,包含無法有效防止神經退化、修復已經退化之神經,現有治療僅僅提高乙醯膽鹼生成,強化大腦功能為目的,並無真正治療之藥物誕世。
阿茲海默症成因眾說紛紜,本研究採用Amyloid-β蛋白假說為依據,該假說提出阿茲海默症是原自於Amyloid-β蛋白異常堆疊造成氧化壓力以及並使突觸失去功能造成神經退化,但現今治療多採用單一目標治療阿茲海默症,在臨床試驗中仍未有良好的結果,因此本研究採用天然萃取物薑黃素作為預防藥物,薑黃素在先前已有大量研究指出具有良好抑制Amyloid-β蛋白生成之功效,同時其本身良好之抗氧化和抗發炎之功效亦具有防止神經退化之功效,同時對於多個目標進行治療,因此採用薑黃素作為預防藥物,但薑黃素本身不易被身體吸收,同時在體內容易降解,導致其生物利用度不佳,因此本研究使用PLGA-PEG-PLGA共聚物製備藥物載體攜載薑黃素,降低薑黃素被降解提高生物利用率,同時利用WST-1證實PLGA-PEG-PLGA具有良好之生物相容性,在人體體溫環境下能形成凝膠,並在體外測試達到25天之控制釋放。 在細胞實驗中,證實所製備薑黃素載體具備抑制Amyloid-β蛋白生成酵素β-secretase之效果,並能有效抑制神經細胞自由基的產生以及降低細胞發炎反應的情況,有效降低Amyloid-β蛋白對於神經細胞的毒性。在動物實驗中,利用鋁誘導動物模型,證實載藥載體具有良好防止阿茲海默症之功效。 | zh_TW |
dc.description.abstract | The World Alzheimer’s report estimated that, in 2015, a new dementia case was diagnosed every 3 seconds and total dementia cases will increase to 131.5 million by 2050. The healthcare cost of dementia worldwide will be 10 trillion. It has been a serious problem that we cannot ignore anymore. Dementia is 60-80 percent caused by Alzheimer (AD). AD is a neurodegenerative disorder of the central nervous system. It will cause cognitive and memory loss. As the result, lots of researches focus on therapy of Alzheimer. However, current therapies just improve cognition but doesn’t prevent neurodegeneration and regenerate neuron which has been degenerative. In other words, there is not a therapy that cure the Alzheimer.
In this research, we based on Amyloid-β (Aβ) hypothesis which indicates Alzheimer is caused by abnormal Aβ accumulation. Aβ will cause oxidative stress, inflammation and neuron dysfunction. Curcumin is a kind of natural extract which has great anti-oxidation and anti-inflammatory ability. Lots of researches showed that curcumin could inhibit Aβ aggregation and disaggregation of Aβ plague. Therefore, we used curcumin as multitarget therapy. However, curcumin can’t be absorbed and will degrade easily. To improve bioavailability, we synthesized PLGA-PEG-PLGA copolymer to prepare a drug delivery system. We used WST-1 assay to prove this copolymer had great biocompatibility. The polymer solution could carry curcumin to improve its water solubility and avoid degradation. In addition, the drug carrier could transform to hydrogel in body temperature and released curcumin until 25 days. Curcumin-load PLGA-PEG-PLGA drug carrier (PGC) showed great result to reduce ROS synthesis in N2a cell and modulate inflammation. PGC also reduced cell-toxicity which caused by Amyloid-β oligomer. It performed excellent properties to protect neuro cell from degradation. By aluminum-induced Alzheimer animal model, we proved PGC could prevent wistar rat from neurodegeneration and memory declining. We estimated that curcumin would inhibit Aβ aggregation and reduce oxidative stress during drug carrier release curcumin. In this research, we expected to develop a drug formulation to prevent Alzheimer up to 20 days. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:06:15Z (GMT). No. of bitstreams: 1 ntu-108-R06548013-1.pdf: 5533581 bytes, checksum: 16a8bb5215d6537c717bba58d01cc22a (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 論文口試委員審定書 i
致謝 ii 摘要 iii ABSTRACT iv 目錄 vi 圖目錄 viii 表目錄 x 縮寫目錄 x 公式目錄 xii 第 1 章 緒論 1 1.1前言 1 1.2阿茲海默症 1 1.2.1 阿茲海默症之症狀 1 1.2.2阿茲海默症之影響因子 2 1.2.3 阿茲海默症之病理特徵 4 1.2.4阿茲海默之成因假說 5 1.2.5阿茲海默症現有治療 10 1.3研究動機 11 第 2 章 文獻回顧 12 2.1天然萃取物用於阿茲海默症治療以及預防 12 2.2薑黃素 (Curcumin) 13 2.3藥物載體 16 2.4聚乳酸-羥基乙酸-乙二醇共聚物 (PLGA-PEG-PLGA) 16 2.5鋁誘導阿茲海默動物模型 19 第 3 章 實驗方法 20 3.1實驗儀器 20 3.2實驗藥品 21 3.3實驗架構 23 3.4材料製備 24 3.5載體性質探討 25 3.6 Aβ蛋白性質分析 28 3.7 In vitro 探討 29 3.8 In vivo 探討 34 3.9統計分析 36 第 4 章 結果討論 37 4.1材料製備鑑定 37 4.2載體性質分析 40 4.3 Aβ蛋白性質探討 46 4.4 In vitro結果探討 48 4.5 In vivo結果探討 54 第 5 章 結論 69 參考文獻 71 | |
dc.language.iso | zh-TW | |
dc.title | 利用溫敏性三嵌段共聚合物PLGA-PEG-PLGA攜載薑黃素應用於阿茲海默症之預防 | zh_TW |
dc.title | Controlled Release of Curcumin-loaded Thermo-sensitive PLGA-PEG-PLGA Hydrogel for Alzheimer Disease Prevention | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 郭士民(Shyh-Ming Kuo),吳造中 | |
dc.subject.keyword | 阿茲海默症,薑黃素,PLGA-PEG-PLGA,溫感凝膠,Amyloid-β蛋白, | zh_TW |
dc.subject.keyword | Alzheimer,curcumin,PLGA-PEG-PLGA,thermosensitive gel,Amyloid-β, | en |
dc.relation.page | 79 | |
dc.identifier.doi | 10.6342/NTU201901878 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-07-25 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
顯示於系所單位: | 醫學工程學研究所 |
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