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研究生: 吳旌豪
Wu, Ching-Hao
論文名稱: 以螢光偏極化技術探討乙醇及膽固醇對陰陽離子液胞雙層膜堅硬度的影響
A Study of Ethanol and Cholesterol Effects on the Bilayer Rigidity of Catanionic Vesicles by Using Fluorescence Polarization Technique
指導教授: 楊毓民
Yang, Yu-Min
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 117
中文關鍵詞: 離子對雙親分子類乙醇體陰陽離子液胞強制製程雙層膜堅硬度螢光偏極化技術膽固醇效應乙醇效應指插
外文關鍵詞: Ion-pair amphiphile, Ethosome-like Catanionic vesicles, Mechanical dispersion fabrication process, Bilayer rigidity, Fluorescence polarization technique, Cholesterol effect, Ethanol effect, Interdigitation
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  • 陰陽離子界面活性劑(或稱離子對雙親分子)具有來源豐富、價格便宜、高化學穩定性及分子可設計性等優點,極有潛力做為製備類脂質體的材料。本研究運用螢光偏極化技術測定由陰陽離子界面活性劑DeTMA-TS (decyltrimethylammonium-tetradecylsulfate, C10-C14) 經強制製程形成的類乙醇體陰陽離子液胞雙層膜的堅硬度,探討膽固醇(0-40%)及乙醇(0-30vol%)的影響及其做為經皮藥物傳輸載體的可行性。由螢光非等向性—溫度圖譜的實驗結果顯示,一般來說,在各個乙醇濃度情況下,膽固醇濃度的增加只會造成陰陽離子液胞雙層膜堅硬度的單調提升。在各個膽固醇濃度情況下,乙醇濃度的增加會造成陰陽離子液胞雙層膜堅硬度降低。 由於膽固醇效應在不同乙醇濃度情況下和乙醇效應在不同膽固醇濃度情況下基準都不同。因此將其影響程度給與正規化。膽固醇對螢光非等向性(r)值所造成的提升,以"rN-CHOL表示" ,其值最高可以達1.984;乙醇對r值所造成的下降,以"rN-EtOH表示" ,其值最低可以達0.782。由此可以得知,膽固醇的作用大於乙醇的作用。 然而,當乙醇濃度大於25 vol % 以及溫度大於40 ℃時,此時的堅硬度會隨著乙醇濃度及溫度的上升,雙層膜堅硬度會有不降反升的結果。推測可能是離子對雙親分子在雙層膜間產生了指插的現象所導致。此外,實驗結果也顯示,膽固醇的添加可以增進液胞穩定性,且加入膽固醇後的DeTMA-TS類乙醇體陰陽離子液胞雙層膜的堅硬度,顯示相對於DPPC (dipalmitoylphosphatidylcholine, C16-C16 ) 乙醇體,具有較小的堅硬度,更適於做為穩定可變形的經皮藥物傳輸載體。

    Due to their abundant sources, low cost, high chemical stability and molecular designability, lipid-like catanionic surfactants (also known as ion-pair amphipliles, IPAs) have emerged as attractive materials to prepare potential vesicular carriers in drug and gene delivery. In this work, bilayer rigidity of ethosome-like catanionic vesicles fabricated from decyltrimethylammonium-tetradecylsulfate (DeTMA-TS) through a forced formation process was systematically studied by using fluorescence polarization technique. By examining ethanol (EtOH,0-30vol%) and cholesterol (CHOL,0-40%) effects on the fluorescence anisotropy (FA) of vesicular bilayers, possible applications of ethosome-like catanionic vesicles as stable and deformable transdermal drug delivery carriers were then evaluated. In general, the experimental FA thermograms showed that FA of ethosome-like catanionic vesicle bilayers as functions of temperature was decreased with increasing ethanol concentration on the one hand, it was monotonically increased with increasing of CHOL concentration on the other hand. Because of the cholesterol effects under different ethanol concentrations and the ethanol effects under different cholesterol concentrations, the benchmarks are different. Therefore, the degree of influence is normalized. The increase induced by cholesterol to the value of fluorescence anisotropy (r) is represented by rN-CHOL, and its value can reach up to 1.984; the decrease induced by ethanol on the value of r is represented by rN-EtOH. The lowest value can reach 0.782. It can be seen that the role of cholesterol is greater than ethanol. In the cases of temperatures higher than 40℃ and EtOH concentrations higher than 25 vol%, however, increase rather than decrease in FA was found and is attributed to the possible interdigitation of ion-pair amphiphile molecules in bilayers. For the optimal formulations, lower bilayer rigidity was exhibited by the stable DeTMA-TS ethosome-like catanionic vesicles as compared with that of dipalmitoylphosphatidylcholine (DPPC) ethosomes. Feasibility of the use of ethosome-like catanionic vesicles is justified.

    摘要 I Extended Abstract III 致謝 XVII 總目錄 XVIII 表目錄 XXI 圖目錄 XXIII 符號 XXIX 第一章 緒論 1 1-1 前言 1 1-2 研究動機與目的 11 第二章 文獻回顧 12 2-1 離子對雙親分子 12 2-2 陰陽離子液胞的形成 14 2-3 液胞的結構與型態 17 2-4乙醇體與類乙醇體陰陽離子液胞 19 2-5 液胞的物理穩定性 23 2-5-1 膽固醇效應 25 2-5-2 乙醇效應 26 2-6 添加劑對液胞雙層膜的特性之影響 28 2-6-1 膽固醇效應 28 2-6-2 乙醇效應 39 2-7 乙醇體在經皮藥物傳輸的應用 44 2-8 螢光偏極化的測量原理 47 第三章 實驗 53 3-1 實驗藥品 54 3-2 實驗儀器及裝置 56 3-2-1 超音波震盪分散裝置 56 3-2-2 動態雷射光散射法粒徑/界面電位分析儀 (Dynamic Light Scattering, DLS) 57 3-2-3 螢光分光光譜儀 (Fluorescence spectrometer) 61 3-2-4 電子控溫裝置 64 3-3 實驗方法 65 3-3-1 離子對雙親分子製備 65 3-3-2 IPA液胞製備 67 3-3-3 粒徑分布、界面電位與液胞存活期的測量 68 3-3-4 液胞雙層膜之螢光偏極化的測定 70 第四章 結果與討論 73 4-1類乙醇體液胞之物理穩定性 74 4-1-1 乙醇效應 74 4-1-2 膽固醇效應 76 4-2 類乙醇體液胞之雙層膜堅硬度-乙醇效應 84 4-2-1 DPH螢光分子在乙醇水溶液中之螢光強度 84 4-2-2 純乙醇效應 86 4-2-3 添加膽固醇之乙醇效應 89 4-3 類乙醇體液胞之雙層膜堅硬度-膽固醇效應 94 4-4 類乙醇體陰陽離子液胞與乙醇體之比較 103 第五章 結論與建議 104 5-1 結論 104 5-2 建議 106 參考文獻 107

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