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研究生: 柯政遠
Ko, Cheng-Yuan
論文名稱: 乙醇體及陰陽體的製備及其包覆/釋放行為之探討
Encapsulation and Release Behavior of Ethosomes and Catansomes Prepared by a Semispontaneous Process
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: 2008
畢業學年度: 96
語文別: 中文
論文頁數: 139
中文關鍵詞: 包覆效率釋放行為陰陽體液胞膽固醇磷脂質乙醇體物理穩定性陰陽離子界面活性劑共溶劑效應
外文關鍵詞: phospholipid, vesicle, cosolvent effect, ethosomes, catanionic surfactant, physical stability, encapsulation efficiency, catansomes, release behavior
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  • 本研究首先製備DeTMA-DS ( decyltrimethylammonium- dodecylsulfate )和DeTMA-TS (decyltrimethylammonium-tetradecylsulfate) 兩種陰陽離子界面活性劑(catanionic surfactant),連同PL-90磷脂質分別做為兩種液胞的材料。應用乙醇的共溶劑效應,採用半自發製程,製備出穩定的陰陽體(catansomes)與乙醇體(ethosomes)。本研究並進一步探討乙醇、膽固醇、液胞材料的濃度對其粒徑、界面電位、物理穩定性的影響。此外,亦以螢光劑CF (5[6] -carboxyfluorescein)做為探測分子,探討陰陽體與乙醇體的包覆效率與釋放行為。
    實驗結果顯示,在緩衝溶液(tris buffer)的環境中,陰陽體較乙醇體有更佳的穩定性。添加適當濃度的乙醇可以有效促進乙醇體與陰陽體的物理穩定性,在20%乙醇濃度下有一最佳值。而膽固醇的添加可以更進一步的提昇其穩定性。在包覆行為的研究上,乙醇體的包覆效率與其粒徑有一正比關係,其攜帶螢光劑CF的方式是以「包覆」為主;陰陽體的包覆效率與膽固醇的含量有一正比關係,其攜帶螢光劑的方式除了「包覆」以外,還有「吸附」 。因此,在本研究中陰陽體的包覆效率可高出乙醇體約4倍以上。在釋放行為的研究上,透過乙醇與膽固醇的濃度可調控釋放速率,乙醇體的釋放半衰期約從一小時至一千小時,陰陽體的釋放半衰期可從數分鐘至數千小時。陰陽體在物理穩定性、包覆效率、控制釋放上的能力上都優於乙醇體,未來更可期待陰陽體成為實用的新型的藥物傳輸載體。

    In a preliminary work, the stable catansomes and ethosomes were prepared from catanionic surfactant (DeTMA-DS , DeTMA-TS), and PL-90 respectively, in the presence of ethanol by the semispontaneous process. A systematic study effects of ethanol, cholesterol and vesicle materials concentrations on the size, zeta-potential, and physical stability. Furthermore, the catansomes and ethosomes were used to encapsulate 5(6) -carboxyfluorescein (CF) in order to investigate the encapsulation and release behavior of catansomes and ethosomes.
    The experimental results suggest catansomes have better physical stability than ethosomes in the buffer solutions, and a optimal ethanol and cholesterol concentration was found to enhance stability of vesicles. The encapsulation efficiency of ethosomes is proportional to size, indicating that the way of ethosomes to carry drugs is through “encapsulation” ; when it comes to catansomes, the encapsulation efficiency is proportional to cholesterol concentrations, indicating the way of cantansomes to carry drugs probably include “encapsulation” and “adsorption”. The release behavior of catansomes shows a controllable wide-ranging release rate by means of ethanol and cholesterol additions.

    摘要 i Abstract iii 誌謝 iv 總目錄 v 表目錄 viii 圖目錄 ix 符號說明 xvi 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 9 2-1 陰陽離子液胞的形成 9 2-2 共溶劑對微脂粒的影響 13 2-3 共溶劑對陰陽離子液胞的影響 18 2-4 液胞的物理穩定性 21 2-5 乙醇對液胞的穩定性之影響 24 2-6 膽固醇對液胞的穩定性之影響 27 2-7 界面活性劑對液胞的破壞效應 29 2-8 液胞的包覆行為 31 2-9 液胞的釋放行為 35 第三章 實驗 38 3-1 實驗藥品 39 3-2 實驗儀器及裝置 41 3-2-1 均質機 41 3-2-2 雷射光散射法粒徑/界面電位分析儀 42 3-2-3 凝膠層析 46 3-2-4 螢光光譜儀 47 3-2-5 穿透式電子顯微鏡 49 3-3 實驗方法 50 3-3-1 陰陽離子界面活性劑(IPA)的製備 50 3-3-2 乙醇體與陰陽體的製備 51 3-3-3 粒徑分布、界面電位與液胞存活期的測量 52 3-3-4 穿透式電子顯微鏡的分析 52 3-3-5 乙醇體與陰陽體的包覆/釋放實驗流程 53 3-3-6 乙醇體與陰陽體對CF的包覆/吸附實驗 57 第四章 結果與討論 59 4-1 乙醇體與陰陽體之特性分析 59 4-1-1 乙醇體之粒徑特性 63 4-1-2 陰陽體之粒徑特性 68 4-1-3 乙醇體之界面電位 71 4-1-4 陰陽體之界面電位 73 4-1-5 乙醇體之物理穩定性 74 4-1-6 陰陽體之物理穩定性 76 4-1-7 乙醇體與陰陽體的TEM影像 78 4-2 包覆藥物對乙醇體與陰陽體的影響 81 4-2-1 包覆藥物對乙醇體的粒徑特性之影響 84 4-2-2 包覆藥物對陰陽體的粒徑特性之影響 86 4-2-3 包覆藥物對乙醇體的界面電位之影響 89 4-2-4 包覆藥物對陰陽體的界面電位之影響 90 4-3 乙醇體與陰陽體的包覆行為 92 4-3-1 凝膠層析之藥物質量平衡 92 4-3-2 乙醇體的包覆行為 96 4-3-3 陰陽體的包覆行為 98 4-4 乙醇體與陰陽體的釋放行為 101 4-4-1 乙醇體的釋放行為 101 4-4-2 陰陽體的釋放行為 103 4-5 乙醇體與陰陽體的比較 107 4-5-1 乙醇體與陰陽體在粒徑特性的比較 107 4-5-2 乙醇體與陰陽體在界面電位的比較 110 4-5-3 乙醇體與陰陽體在物理穩定性的比較 115 4-5-4 乙醇體與陰陽體在包覆行為的比較 115 4-5-5 乙醇體與陰陽體在釋放行為的比較 117 第五章 結論與建議 120 5-1 結論 120 5-2 建議 123 參考文獻 124 自述 139

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