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研究生:張詰苡
研究生(外文):Chieh-YiChan
論文名稱:以螢光非等向性方法檢視類乙醇體陰陽離子液胞的雙層膜堅硬度-乙醇及膽固醇效應探討
論文名稱(外文):Examining bilayer rigidity of ethosome-like catanionic vesicles containing cholesterol by using the fluorescence anisotropy method-Ethanol and cholesterol effects
指導教授:楊毓民楊毓民引用關係
指導教授(外文):Yu-Min Yang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學工程學系
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:中文
論文頁數:92
中文關鍵詞:陰陽離子界面活性劑類乙醇體陰陽離子液胞經皮藥物傳輸半自發製程雙層膜堅硬度螢光非等向性方法乙醇效應膽固醇效應液胞穩定性
外文關鍵詞:Catanionic surfactantCatanionic vesicleTransdermal drug deliverySemi-spontaneous fabrication processBilayer rigidityFluorescence anisotropyEthanol effectCholesterol effectVesicle stability
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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。本研究運用螢光非等向性方法測定由陰陽離子界面活性劑DeTMA-TS (decyltrimethylammonium-tetradecylsulfate, C10-C14)經半自發製程形成的類乙醇體陰陽離子液胞雙層膜的堅硬度,檢視乙醇及膽固醇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實驗結果顯示,一方面增加乙醇濃度可以降低類乙醇體陰陽離子液胞的雙層膜堅硬度;另一方面增加膽固醇濃度則會提升雙層膜的堅硬度。本研究也探討乙醇及膽固醇對類乙醇體陰陽離子液胞穩定性的影響,結果顯示,膽固醇可以有效提升類乙醇體陰陽離子液胞的穩定性,並擴展乙醇共溶劑使用的濃度範圍。本研究並進一步測定在最適化配方組成下的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 semi-spontaneous process was systematically studied by using fluorescence polarization technique . By examining ethanol and cholesterol (CHOL) effects on the fluorescence anisotropy (FA) of vesicular bilayers and physical stability of vesicles, possible applications of ethosome-like catanionic vesicles as stable and deformable transdermal drug delivery carriers were then evaluated. The experimental FA thermograms showed that FA of ethosome-like catanionic vesicle bilayers was decreased with increasing ethanol concentration on the one hand, it was monotonically increased with increasing of CHOL concentration on the other hand. Moreover, addition of CHOL was found to effectively enhance the physical stability and broaden the ethanol concentration window of ethosome-like catanionic vesicles. 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 II
總目錄 XVI
表目錄 XIX
圖目錄 XXI
第一章 緒論 1
1-1 前言 1
1-2 研究動機與目的 8
第二章 文獻回顧 10
2-1 陰陽離子界面活性劑 10
2-1-1陰陽離子液胞的形成 11
2-1-2陰陽離子液胞的結構型態 13
2-2 乙醇體 15
2-3 乙醇體的物理穩定性 17
18
2-3-1 乙醇效應 19
2-3-2 膽固醇效應 21
2-4 乙醇體的雙層膜特性 22
2-4-1 乙醇效應 22
2-4-2 膽固醇效應 26
2-5 乙醇體在經皮藥物傳輸的應用 29
2-6 螢光非等向性測量原理 31
第三章 實驗 33
3-1 實驗藥品 34
3-2 實驗儀器及裝置 36
3-2-1 均質機 (Homogenizier) 36
3-2-2 動態雷射光散儀 (Dynamic Light Scattering, DLS) 37
3-2-3 螢光光譜儀 41
3-2-4 電子控溫裝置 44
3-3 實驗方法 45
3-3-1 陰陽離子界面活性劑 (IPA) 製備 45
3-3-2 類乙醇體陰陽離子液胞的製備 46
3-3-3 粒徑分布、界面電位與液胞存活期的測量 47
3-3-4 液胞雙層膜之螢光非等向性的測量 49
第四章 結果與討論 50
4-1 類乙醇體液胞之物理穩定性 51
4-1-1 陰陽離子界面活性劑 (IPA) 之濃度影響 51
4-1-2 水溶液與緩衝溶液之比較 54
4-1-3 乙醇效應 58
4-1-4 膽固醇效應 60
4-2 類乙醇體液胞之雙層膜堅硬度-乙醇效應 65
4-2-1 純乙醇效應 65
4-2-2 添加膽固醇之乙醇效應 69
4-3 類乙醇體液胞之雙層膜堅硬度-膽固醇效應 73
4-4 類乙醇體陰陽離子液胞與乙醇體之比較 78
第五章 結論與建議 81
5-1 結論 81
5-2 建議 83
參考文獻 84
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