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研究生: 林聖鈞
Sheng-Jiun Lin
論文名稱: 二維二硫化鎢/高分子複合材料之製備及其於電誘導經皮藥物釋放
Preparation of Two - dimensional Tungsten Disulfide / polymer Composites and electrical induction percutaneous drug release
指導教授: 蔡協致
Hsieh-Chih Tsai
口試委員: 蕭百芬
鄭智嘉
林宣因
學位類別: 碩士
Master
系所名稱: 應用科技學院 - 應用科技研究所
Graduate Institute of Applied Science and Technology
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 84
中文關鍵詞: 二硫化鎢層狀電刺激藥物釋放
外文關鍵詞: WS2, Layered, Electrically Stimuli, Drug Release
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近年來,過渡金屬硫族化合物如二硫化鉬(MoS2)、二硫化鎢(WS2)等單層之二維半 導體材料,因具有獨特的光電特性並在單層時導電性最佳,在層狀的應用受到了學術界 的高度重視,成為當前研究的熱點材料之一。二維奈米材料是二維層狀材料在奈米級厚 度的薄片狀材料,具有優異的光學、熱學、電學、機械學方面的特性。電誘導具有良好 的可控性並允許精確控制藥物釋放的性質可以運用於藥物傳遞上。本研究使用半導體二 硫化鎢來製備此複合型藥物載體。使用三種不同的硫醇(TGA、Mercaptosuccinic acid、 2-Ethanethiol)並把各種硫醇分三種不同重量比例來對二硫化鎢進行剝層,並探討各種硫 醇對二硫化鎢之剝層上何種較佳,由拉曼光譜儀測量得知三種剝層效果差異不大,並於 剝層後的二硫化鎢包覆藥物(5-Fluorouracil),並由拉曼光譜儀分析 5-Fluorouracil 於二硫 化鎢層狀上之分佈,證實二硫化鎢層狀上確實可攜載 5-Fluorouracil 的存在。而藥物含 量的量測可由紫外-可見光光譜計算,結果顯示 2-Ethanethiol 修飾的二硫化鎢可攜載較 多的藥物。目前初步電誘導藥物釋放實驗顯示,我們可以藉由施加小幅電量來達到提升 藥物釋放效果。


Stimuli-responsive or “smart” biomaterials are of great interest in the field of biotechnology and biomedicine. Drug delivery system based on external stimulus-responsive materials for controlled and long-term drug release under an action external action offer the promising of new treatment. Here we present, electrically triggered drug release form WS2 nanocomposite composed of two dimensional materials integrate with conducting polymer such as polypyrole. In this study, three thiol compounds was used to study the exfoliation of WS2. The exfoliation of WS2 few layers were characterized by Raman and Uv-vis spectrum. In addition, the polypyrole was then added in the exfoliated WS2. The current results showed that therapeutic molecule only released from nanocomposite, no passive drug release is expected. Currently, we still continue to utilize the ultrasound waves to reduce the size decrease the height of the WS2 nanosheet to enhanced drug loading in system to achieve enhanced drug release.

摘要 .................................................................... I Abstract ............................................................... II 總目錄 ................................................................ III 圖目錄 .................................................................. V 表目錄 ................................................................ VII 第一章 前言 .......................................................... 1 1.1 研究動機和目的........................................................... 1 第二章 文獻回顧 ...................................................... 3 2.1 智能藥物輸送系統及其臨床潛力 ............................................ 3 2.2 智能藥物遞奈米平台的設計理論 ............................................ 3 2.3 不同刺激應答奈米平台 ................................................... 4 2.3.1 pH 應答............................................................... 5 2.3.2 氧化還原應答 ......................................................... 6 2.3.3 酶應答 ............................................................... 6 2.3.4 溫度應答 ............................................................. 7 2.3.5 光、磁和超聲應答 ..................................................... 7 2.3.6 其他應答系統 ......................................................... 8 2.3.7 電刺激應答 ........................................................... 9 2.4 智能奈米級 DDS........................................................... 9 2.5 二維材料 ............................................................... 11 2.5.1 二維材料的介紹 ...................................................... 11 2.5.2 二維材料的結構 ...................................................... 12 2.5.3 二維材料的特性 ...................................................... 18 2.5.4 過渡金屬二硫化物(TMD)特性 ........................................... 18 2.5.5 過渡金屬二硫化鎢(WS2)介紹............................................ 24 2.6 皮膚構造及經皮吸收...................................................... 25 ............................................................ 25 ........................................................ 29 第三章 實驗方法 ..................................................... 30 3.1 實驗藥品及耗材.......................................................... 30 3.2 實驗儀器 ............................................................... 34 3.2.1 紫外-可見光光譜儀(Ultraviolet-Visible Spectroscopy,UV/Vis) ......... 35 3.2.2 粒徑及電位分析儀(Dynamic Light Scattering,DLS) ..................... 35 3.2.3 拉曼光譜儀(Raman).................................................... 36 2.6.1 皮膚構造 2.6.2 皮膚吸收途徑 III 3.2.4 穿透式電子顯微鏡(Electron Eicroscope,TEM) ......................... 36 3.2.5 原子力顯微鏡(Atomic Force Microscope,AFM) ......................... 36 3.2.6 X-射線繞射分析 (XRD) ................................................ 37 3.2.7 高效液相色譜法(High Performance Liquid Chromatography,HPLC) ......... 37 3.2.8 體外電誘導藥物釋放設計 .............................................. 38 3.3 實驗流程 ............................................................... 39 3.4 實驗過程 ............................................................... 40 3.4.1 WS2 表面改質與分層 .................................................. 40 3.4.2 分層後二硫化鎢與 Polypyrrole......................................... 41 3.4.3 藥物包覆 ............................................................ 42 3.4.4 電誘導藥物釋放設計 .................................................. 43 3.4.5 裸鼠皮膚電刺激實驗 .................................................. 44 第四章 結果與討論 ...................................................... 45 4.1 二硫化鎢表面改質與分層之鑑定 ........................................... 45 4.1.1 二維 WS2 粒徑及電位量測 ............................................... 45 4.1.2 二維 WS2 之紫外及可見光譜分析 ......................................... 47 4.1.3 二維 WS2 之拉曼光譜分析 ............................................... 49 4.1.4 二維 WS2 之電子顯微鏡分析 ............................................. 51 4.1.5 二維 WS2 之原子力顯微鏡分析 ........................................... 52 4.1.6 二維 WS2 之 X 光繞射分析 ............................................... 53 4.2 藥物包覆 ............................................................... 54 4.2.1 5-Fu 藥物濃度檢量線.................................................. 54 4.2.2 5-Fu 包覆量.......................................................... 55 4.2.3 藥物於複合材料分佈成像............................................... 56 4.3 體外電誘導藥物釋放...................................................... 58 4.4 動物實驗 ............................................................... 59 4.4.1 螢光顯微鏡........................................................... 59 4.4.2 拉曼光譜分佈分析..................................................... 62 4.4.3 高效液相色譜法定量分析............................................... 63 第五章 結論 ............................................................ 65 第六章 參考文獻 ....................................................... 66

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