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研究生: 王鈺婷
Wang, Yu-Ting
論文名稱: 帶負電陰陽離子液胞的物化特性及維他命E醋酸酯包覆效率-離子對雙親分子碳鏈結構的影響
Physicochemical properties and vitamin E acetate encapsulation efficiency of negatively charged catanionic vesicles: Effects of alkyl chain structure of ion pair amphiphile
指導教授: 張鑑祥
Chang, Chien-Hsiang
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: 2015
畢業學年度: 103
語文別: 中文
論文頁數: 117
中文關鍵詞: 陰陽離子液胞離子對雙親分子相轉移行為維他命E醋酸酯包覆效率
外文關鍵詞: catanionic vesicle, encapsulation efficiency, ion pair amphiphile, phase transition behavior, vitamin E acetate
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  • 本研究分別以由陽離子型界面活性劑hexadecyltrimethylammonium bromide(HTMAB)、tetradecyltrimethylammonium bromide (TTMAB)、dodecyltrimethylammonium bromide(DTMAB)與陰離子型界面活性劑sodium hexadecylsulfate(SHS)、sodium dodecylsulfate(SDS)所形成之四種不同碳鏈長度的離子對雙親分子(ion pair amphiphile, IPA)HTMA-HS, HTMA-DS, TTMA-DS及DTMA-DS為主材料,並添加雙十六烷基磷酸鹽(dihexadecyl phosphate, DHDP)及膽固醇,以強制性製程製備出帶負電之陰陽離子液胞(catanionic vesicle),探討不同的IPA碳鏈結構對於液胞物理特性、雙層膜流動性,以及維他命E醋酸酯之包覆效率的影響。
    實驗結果顯示,就等莫耳比例混合之IPA及DHDP所製備出的液胞分散液而言,由短碳鏈的DTMA-DS與TTMA-DS所形成之液胞的物理穩定性較低,應是IPA與DHDP之分子間凡得瓦作用不足所致。隨著膽固醇含量的提高,混合IPA/DHDP/膽固醇所形成之液胞的穩定天數皆呈現增加之趨勢,表示膽固醇的添加能有效提升液胞之物理穩定性。
    以螢光偏極化分析液胞雙層膜的流動性,在固定膽固醇添加比率下,隨著IPA碳鏈長度增加,混合IPA/DHDP/膽固醇所形成之液胞的雙層膜流動性有下降的趨勢,此歸因於長碳鏈IPA之間具有較強的凡得瓦作用。此外,在四種IPA/DHDP混合系統中添加膽固醇,在高溫時皆使得雙層膜流動性變低,在低溫時雙層膜流動性的變化則較不顯著,此為膽固醇結構所誘導出之規則效應以及不規則效應在不同溫度區間的影響程度不同所導致。整體而言,膽固醇的添加能抑制IPA/DHDP/膽固醇液胞雙層膜的相轉移行為,此可應用於控制液胞的包覆及釋放行為。
    各IPA/DHDP/膽固醇液胞系統在包覆維他命E醋酸酯後,液胞粒徑皆些微增大,這可能和維他命E醋酸酯能成功包覆於液胞雙層膜內有關。此外,包覆維他命E醋酸酯可以增加液胞之物理穩定性,應是其結構與膽固醇相似,固環部分能限制分子之疏水碳氫鏈的自由度而穩定液胞雙層膜的結構。在同樣的膽固醇添加比率下,不同的IPA碳鏈結構會影響所形成之液胞對於維他命E醋酸酯的包覆效率,其中HTMA-DS/DHDP/膽固醇液胞系統的包覆效率最低,其餘三種IPA/DHDP/膽固醇液胞系統則差異不大,原因應與不同IPA結構所產生雙層膜的疏水體積、雙層膜流動性的差異,以及維他命E醋酸酯在雙層膜中的排列有關。

    In this study, four ion pair amphiphiles (IPAs) with different alkyl chain structures, hexadecyltrimethylammonium-hexadecylsulfate (HTMA-HS), hexadecyltrimethyl- ammonium-dodecylsulfate (HTMA-DS), tetradecyltrimethylammonium-dodecylsulfate (TTMA-DS), and dodecyltrimethylammonium-dodecylsulfate (DTMA-DS), were prepared from corresponding mixed cationic/anionic surfactant systems. Physical properties, membrane fluidity, and vitamin E acetate encapsulation efficiency of negatively charged catanionic vesicles fabricated from IPA, dihexadecyl phosphate (DHDP), and cholesterol by forced formation approach were then investigated. The strong van der Waals interaction between IPA and DHDP played an important role in the enhancement of physical stability of mixed IPA/DHDP catanionic vesicles. Fluorescence polarization analysis indicated that at a constant mole fraction of cholesterol, the membrane fluidity of the IPA/DHDP/cholesterol vesicles decreased with increasing the alkyl chain length of IPA. It was found that the vitamin E acetate encapsulation efficiency of the HTMA-DS/DHDP/cholesterol vesicle was lowest among the four IPA/DHDP/cholesterol vesicles, which was ascribed to the difference in the lipophilic volume, fluidity of the vesicular bilayers, and arrangement of vitamin E acetate in bilayers.

    摘要 I Extended Abstract III 誌謝 X 表目錄 XIV 圖目錄 XVI 符號說明 XXII 第一章 緒論 1 1-1 前言 1 1-2 文獻回顧 4 1-2-1 離子對雙親分子 4 1-2-2 陰陽離子液胞 5 1-2-3 帶電液胞 6 1-2-4 膽固醇效應 8 1-2-5 疏水性藥物的包覆 11 1-2-6 液胞的相轉移行為 13 1-2-7 碳鏈對稱性和鏈長的效應 16 1-3 研究動機與目的 18 第二章 實驗 19 2-1 藥品 19 2-2 實驗儀器及裝置 20 2-2-1 超音波震盪分散裝置 20 2-2-2 雷射光散射法粒徑及界面電位分析儀 20 2-2-3 元素分析儀 24 2-2-4 穿透式電子顯微鏡 25 2-2-5 凝膠層析管 25 2-2-6 高效能液相層析儀 26 2-2-7 發光光譜儀 27 2-3 實驗方法 27 2-3-1 離子對雙親分子的製備 27 2-3-2 液胞分散液的製備 29 2-3-4 維他命E醋酸酯包覆效率的計算 31 2-3-5 螢光偏極化實驗 32 第三章 結果與討論 33 3-1 HTMA-HS液胞分散液的製備 33 3-2 HTMA-HS/DHDP之液胞分散液 36 3-3 膽固醇效應 39 3-3-1 HTMA-HS/DHDP/膽固醇之陰陽離子液胞的物理特性 39 3-3-2 液胞雙層膜的流動性及相轉移行為 45 3-4 包覆維他命E醋酸酯的液胞 57 3-5 陰陽離子對雙親分子碳鏈結構的效應 66 3-5-1 IPA/DHDP/膽固醇之陰陽離子液胞的物理特性 66 3-5-2 IPA/DHDP/膽固醇之陰陽離子液胞雙層膜的相轉移行為 77 3-5-3 維他命E醋酸酯之包覆效率 88 第四章 結論 100 參考文獻 102

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