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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 牙醫專業學院
  4. 口腔生物科學研究所
Please use this identifier to cite or link to this item: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82719
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???org.dspace.app.webui.jsptag.ItemTag.dcfield???ValueLanguage
dc.contributor.advisor李伯訓(Bor-Shiunn Lee)
dc.contributor.authorDe-Hao Laien
dc.contributor.author賴德豪zh_TW
dc.date.accessioned2022-11-25T07:58:26Z-
dc.date.copyright2021-11-09
dc.date.issued2021
dc.date.submitted2021-10-27
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82719-
dc.description.abstract"口腔癌名列癌症十大死因之一,目前的治療方式以手術、放射線、化療為主,手術切除為最常用的治療,但切除的範圍如果較大容易造成患者外觀與功能上的損害,因此常配合化療藥物的使用,然而化療藥物大多使用高劑量殺死癌細胞,容易造成嚴重之副作用。 cisplatin(順鉑)作為抗癌藥物被廣泛運用在臨床治療,然而cisplatin具有許多副作用,如腎毒性、神經毒性等。為了有效地降低cisplatin帶來的負面影響,本研究將cisplatin包覆在幾丁聚醣奈米載體中,透過動態光散射分析儀(Dynamic light scattering)進行奈米粒子粒徑及表面電位分析,並以穿透式電子顯微鏡(Transmission electron microscope)觀察粒子型態,完成基本性質檢測後,探討不同chitosan:TPP質量比對藥物包覆率及釋放率的影響,使用紫外線/可見光分光光譜儀檢測藥物含量。細胞實驗方面使用口腔癌細胞SAS (human tongue squamous-cell carcinoma cell)進行模擬,經過細胞活性檢測(MTT assay)觀察奈米粒子對癌細胞的毒殺效果。 為了使奈米粒子在特定時間進入患部,我們將粒子與感溫性水凝膠混合,期望水凝膠在接近人體溫度時相轉變,將奈米粒子擠出,接著利用其帶正電的特性,以電化學離子導入法(iontophoresis)將其導入癌組織,且皮膚或黏膜層帶負電,具有陽離子滲透性,能促進抗癌藥物導入癌組織,期望病變區可以縮小,再用手術方式切除,此法不但能降低化療藥物的劑量,也能提升化療藥物對癌組織的專一性,以造福更多的患者。 結果顯示,chitosan:TPP質量比 = 15:1的奈米粒子有較佳的包覆率及緩釋放效果,在細胞毒殺效果上,雖然不同chitosan:TPP質量比的奈米粒子在第5天最大濃度的細胞毒殺效果似乎都是能抑制約2成的癌細胞,但考慮到長期緩釋放效果,仍選擇藥物可以持續釋放約一個月的chitosan:TPP質量比 = 15:1奈米粒子進行電導入試驗。 電導入試驗裝置分為有玻璃槽及無玻璃槽2種,變動電流組(0 <-> 1.5 mA, 2h)為最佳組別,高達10.59 µg/mL的cisplatin能滲透進皮下直至癌組織,其藥量高於cisplatin的IC50 (half maximal inhibitory concentration)值。找出最佳電滲透參數後,為了符合後續臨床動物實驗的應用,我們將玻璃槽拿掉,改以無玻璃槽之電化學裝置架接,作為最佳電滲透組別的DPV 63 cycles, Ei=1.5 V, 2h (變動電壓組)有高達6.74 µg/mL的cisplatin能滲透進豬皮,6.74 µg/mL的cisplatin足以抑制約50 %的癌細胞。整體來說,變動電壓組比變動電流組有更好的電導入效率,其中又以DPV 63 cycles, Ei=1.5 V, 2h (變動電壓組)有最佳的電導入效率。"zh_TW
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dc.description.tableofcontents"口試委員會審定書 i 致謝 ii 摘要 iii ABSTRACT v 目錄 vii 圖目錄 x 表目錄 xiii Chapter 1 緒論 1 Chapter 2 文獻回顧 2 2.1 口腔癌 2 2.2 順鉑(cisplatin) 2 2.3 奈米粒子 4 2.4 高分子奈米粒子 4 2.5 幾丁聚醣 5 2.5.1 幾丁聚醣黏膜附著性 6 2.5.2 Tight junction 6 2.6 三聚磷酸鈉 (Sodium triphosphate) 7 2.7 乳化法 7 2.8 溫感性水凝膠 8 2.9 UV光接枝聚合 9 2.10 離子電滲療法(Iontophoresis) 10 2.10.1 計時電流法(Chronopotentiometry, CP) 11 2.10.2 微分脈衝伏安法(Differential Pulse Voltammetry, DPV) 13 Chapter 3 材料方法 15 3.1 實驗藥品 15 3.2 實驗儀器 20 3.3 實驗流程圖 21 3.4 幾丁聚醣/順鉑(Chitosan/Cisplatin Cisplatin)奈米粒子製備 22 3.5 奈米粒子基本特性檢測 23 3.5.1 動態光散射分析儀(Dynamic Light Scattering, DLS) 23 3.5.2 穿透式電子顯微鏡(Transmission electron microscope, TEM) 24 3.6 奈米粒子藥物包覆率及控制釋放 24 3.6.1 Cisplatin檢量線製備 24 3.6.2 奈米粒子藥物包覆率計算 25 3.6.3 奈米粒子藥物釋放 25 3.7 細胞培養及藥物測試 26 3.7.1 細胞培養液配製 26 3.7.2 解凍細胞 26 3.7.3 細胞繼代培養 27 3.7.4 冷凍細胞 27 3.8 細胞活性測試 (MTT Assay) 28 3.8.1 MTT溶液配製 28 3.8.2 Chitosan/Cisplatin奈米粒子抗癌效果測試 28 3.9 水膠製備 29 3.10 Iontophoresis離子導入法 29 3.10.1 豬皮組織前製處理 33 3.10.2 電化學裝置架接 33 3.10.3 無玻璃槽之電化學裝置架接 35 Chapter 4 實驗結果 37 4.1 Chitosan/Cisplatin奈米粒子基本性質分析結果 37 4.1.1 動態光散射分析儀(DLS) 37 4.1.2 穿透式電子顯微鏡(TEM) 37 4.2 Chitosan/Cisplatin奈米粒子最佳條件分析結果 38 4.2.1 不同Chitosan:TPP質量比對包覆率影響之探討 38 4.2.2 不同Chitosan:TPP質量比對藥物釋放影響之探討 38 4.3 細胞活性測試(MTT Assay)結果 40 4.3.1 不同Chitosan : TPP質量比之奈米粒子對抗癌細胞效果影響之探討 40 4.4 Chitosan/Cisplatin奈米粒子之電導入試驗結果 42 Chapter 5 討論 66 Chapter 6 結論 73 Chapter 7 參考資料 74"
dc.language.isozh-TW
dc.subject奈米粒子zh_TW
dc.subject水凝膠zh_TW
dc.subject幾丁聚醣zh_TW
dc.subject順鉑zh_TW
dc.subject口腔癌zh_TW
dc.subject離子導入法zh_TW
dc.subjecthydrogelen
dc.subjectnanoparticleen
dc.subjectchitosanen
dc.subjectcisplatinen
dc.subjectoral canceren
dc.subjectiontophoresisen
dc.title以電化學反應促進口腔癌貼片之藥物滲透效率zh_TW
dc.titlePromote the penetration efficiency of anti-oral cancer patches by electrochemical reactionen
dc.date.schoolyear109-2
dc.description.degree碩士
dc.contributor.oralexamcommittee張哲政(Hsin-Tsai Liu),陳漪紋(Chih-Yang Tseng)
dc.subject.keyword口腔癌,順鉑,幾丁聚醣,奈米粒子,水凝膠,離子導入法,zh_TW
dc.subject.keywordoral cancer,cisplatin,chitosan,nanoparticle,hydrogel,iontophoresis,en
dc.relation.page83
dc.identifier.doi10.6342/NTU202103636
dc.rights.note未授權
dc.date.accepted2021-10-27
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept口腔生物科學研究所zh_TW
dc.date.embargo-lift2024-11-01-
Appears in Collections:口腔生物科學研究所

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