臺灣博碩士論文加值系統

本文以四種陰陽離子界劑DP-DS（12C-12C）、CP-DS（16C-12C）、DTMA-DS（12C-12C）、HTMA-DS（16C-12C）取代傳統脂質，利用「強制性」方式來製備液胞，以探討陰陽離子液胞的穩定性和膽固醇的添加效應。文中利用螢光劑CF和蛋白質酵素beta-galactosidase兩種包覆物，觀察四種陰陽離子界劑在添加膽固醇之後的包覆特性，並針對作為傳輸載體的可能性做一番探討。在液胞穩定性的探討上，以雷射光散射法粒徑測定儀，測定液胞的粒徑分佈及其隨時間的變化。而在液胞的包覆行為方面，是利用螢光光譜儀，對被包覆之螢光試劑（CF）及蛋白質酵素（beta-galactosidase），進行包覆量及洩漏的觀測。
對於陰陽離子界劑所製備液胞的穩定性實驗結果發現，液胞的穩定性主要由碳氫鏈中碳數所主導。對稱性越好的系統，其構成的液胞越穩定，而親水頭基對液胞的穩定效應並不明顯。而由膽固醇添加的實驗結果可知，膽固醇對陰陽離子液胞的穩定性有顯著的增強效應，且碳鏈對稱性越好的系統中，所需膽固醇的量越少。在液胞的包覆實驗上發現，此四系統對螢光劑和蛋白質酵素的包覆效率最高可達21.6%和10.2％。而包覆效率的大小主要與陰陽離子界劑的頭基有關，與碳鏈長短及對稱性無明顯之關係。然而包覆物的洩漏率則受碳鏈所控制，碳鏈對稱性越佳，液胞穩定性越好的系統，其洩漏率越低。

Four kinds of catanionic surfactants including DP-DS, CP-DS, DTMA-DS, HTMA-DS were used to prepare vesicles by method of reverse-phase evaporation. The effects of head group and chain length of the catanionic surfactants, as well as the effects of cholesterol incorporation, on the stability of vesicles were studied. These vesicles were than used to encapsulate carboxyfluorescein（CF）and beta-galactosidase to evaluate the possibility of these vesicles to be used as carriers. The size distribution of vesicles were measured by laser light scattering and the entrapment and release of CF and beta-galactosidase were determined by a fluorescence spectrophotometer.
The results show that the stability of vesicles is strongly related to the symmetry and length of hydrocarbon chains. The more symmetrical system（12C-12C）exhibits a more stability of the vesicles. When cholesterol is incorporated, the vesicles become stable and the stability increases with the increasing amount of cholesterol. From the experimental results of entrapment, it was found that the entrapment efficiency is mainly affected by the head groups of catanionic surfactants. The maximum values of entrapment efficiency for CF and beta-galactosidase in the four systems are about 21.6％ and 10.2％ respectively. The leakage rate of the entrapped material has intimated relationship with stability of vesicles. The more symmetrical and stable the vesicles are, the smaller the leakage rate is obtained.

目錄
中文摘要 I
英文摘要 II
誌謝 III
目錄 IV
表目錄 VII
圖目錄 VIII
符號說明 XII
第一章 諸論 1
1- 1前言 1
1-1-1 傳統卵磷脂液胞於藥物釋放上的應用 1
1-1-2 陰陽離子界劑液胞的應用與藥物釋放上的可行性 2
1-1-3 研究動機與目的 4
1-2文獻回顧 4
1-2-1 傳統卵磷脂液胞的結構、型態與特性 4
1-2-2 陰陽離子界劑液胞的結構、型態與特性 6
1-2-3 膽固醇穩定液胞的機制 7
1-2-4 螢光劑CF的包覆 9
1-2-5 蛋白質酵素的包覆 10
1-2-6 Triton X-100對液胞的破壞效應 10
第二章 實驗 17
2-1 藥品 17
2-2 儀器及實驗裝置 18
2-2-1 超音波震盪分散裝置 18
2-2-2 雷射光散射法粒徑測定儀 18
2-2-3 螢光光譜儀 19
2-3 實驗步驟 19
2-3-1陰陽離子界劑液胞的製備 19
2-3-1-1 固體沈澱物的製備 19
2-3-1-2 未含包覆物液胞的製備 20
2-3-1-3 添加膽固醇液胞的製備 20
2-3-1-4 包覆螢光劑液胞的製備 20
2-3-1-5 包覆蛋白質酵素液胞的製備 21
2-3-2管柱分離時間的量測 22
2-3-3 液胞粒徑量測 22
2-3-4 螢光校正曲線量測 23
2-3-5 蛋白質酵素活性量測 24
2-3-6 液胞包覆效率量測 25
2-3-6-1 包覆螢光劑 25
2-3-6-2 包覆蛋白質酵素 25
2-3-7 液胞包覆螢光劑的洩漏率量測 25
第三章 結果與討論 .. 36
3-1 膽固醇添加對陰陽離子液胞穩定性的影響 36
3-1-1 膽固醇添加前的穩定性 36
3-1-1-1 CP-DS與DP-DS系統的液胞穩定性 36
3-1-1-2 HTMA-DS與DTMA-DS系統的液胞穩定性 37
3-1-2 膽固醇添加後的穩定性 38
3-1-2-1 未包覆物之液胞的粒徑量測結果 38
3-1-2-2 包覆螢光劑液胞的粒徑量測結果 41
3-1-2-3 包覆蛋白質酵素液胞的粒徑量測結果 41
3-2 陰陽離子液胞的包覆特性 42
3-2-1 包覆效率 42
3-2-2 洩漏率 43
第四章 結論 85
建議 86
參考文獻 87
自述 92

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