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研究生: 周宗翰
Tzung-Han Chou
論文名稱: 微脂粒藥物釋放系統界面性質之研究
The study of interficial properties of liposomal drug systems
指導教授: 朱一民
I-Ming Chu
口試委員:
學位類別: 博士
Doctor
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2002
畢業學年度: 91
語文別: 中文
論文頁數: 142
中文關鍵詞: 微脂粒混合單分子層等溫線壓縮係數鬆弛行為紫杉醇界面性質穩定性
外文關鍵詞: liposomes, mixed monolayers, isotherm, compressibility, relaxation behavior, paclitaxel, interficial properties, stability
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  • 本研究主要是藉由氣/液界面混合單分子層界面性質之研究幫助了解分子間的交互作用。在不同溫度下,分別進行Distearoyl- phosphatidylcholine (DSPC)/cholesterol,DSPC/Distearoylphosphatidyl- ethanolamine-poly(ethylene glycol)2000(DSPE-PEG2000),DSPC/paclitaxel 混合單分子層,DSPC/cholesterol/DSPE-PEG2000混合單分子層,以及DSPC/cholesterol/DSPE-PEG2000/paclitaxel混合單分子層表面壓-每分子佔據面積(□□A)等溫線之量測。□□A等溫線顯示這四種成分在24.5℃下氣/液界面是互相混合的。藉由所獲得之數據可進行這些混合系統氣/液界面熱力學特徵的研究。溫度與組成兩者對於混合單分子層的等溫線形狀,可壓縮性,面積鬆弛行為以及穩定性均會有顯著的影響。最穩定的配方可結由混合過剩自由能的估算來決定。除此之外,這些混合系統微脂粒膜的穩定性則是藉由微脂粒包覆5,6-carboxyfluorescein(CF)的釋放實驗來判斷。最後,本研究對於這些混合單分子層的發現與他們在微脂粒中的行為也進行了進一步的探討。


    This study is primarily concerned with the molecular interaction and the interfacial properties of mixed monolayers at the air/water interface at different temperatures. Measurement of surface pressure □□area per molecule (□□A) isotherms for DSPC/cholesterol, DSPC/DSPE-PEG2000, DSPC/paclitaxel, mixed monolayers, DSPC/cholesterol/DSPE-PEG2000 mixed monolayers, and DSPC/cholesterol/DSPE-PEG2000/paclitaxel mixed monolayers, respectively were conducted at different temperatures. Thermodynamic characteristics of these mixed systems at the air/water interface were studied from data obtained. The □□A isotherms showed these four components were miscible at 24.5℃. Temperature and compositions both had profound influence on the shape of isotherms, the compressibility, the stability, and the relaxation behavior of mixed monolayers. The most stable formulation can be determined by the estimation of the excess free energy of mixing. Additionally, the corresponding liposomal membrane stability of these mixed system was determined by release of encapsulated 5,6-carboxyfluorescein. Finally, the relevance of the observations for these mixed monolayers to the behavior in a liposomal domain was discussed.

    目錄 中文摘要 I 英文摘要 II 目錄 III 表目錄 VIII 圖目錄 IX 第一章 簡介 1 1.1 研究動機與目的 1 1.2 單分子層表面壓□每分子佔據面積(□□A)等溫線量測的基本原理 5 1.3 單分子層與脂雙層的關聯性 8 第二章 實驗 10 2.1 藥品及材料 10 2.2 儀器及方法 13 2.2.1單分子層溶液的製備 13 2.2.2 側面表面壓之量測 13 2.2.3 鬆弛實驗 14 2.2.4 CF-微脂粒的製備 14 2.2.5 微脂粒CF釋放的量測 15 2.2.6 Paclitaxel-微脂粒的製備 16 2.2.7 Paclitaxel的包覆效率 17 第三章 理論分析 18 3.1 過剩面積的分析 18 3.2 混合自由能及過剩自由能的分析 18 3.3 等溫壓縮係數的分析 19 第四章 DSPC/Cholesterol 混合系統 20 引言 20 結果與討論 21 4.1 表面壓-每分子佔據面積等溫線(□□A isotherm) 22 4.2 混合度及過剩面積之分析 25 4.3 單分子層的穩定性 33 4.4 可壓縮係數及混合單分子層的鬆弛行為 40 4.5單分子層系統與微脂粒系統的關連性 43 結論 45 第五章 DSPC/DSPE-PEG2000混合系統 47 引言 47 結果與討論 48 5.1 表面壓-每分子佔據面積等溫線(□□A isotherm) 48 5.2 混合單分子層的熵變化和潛熱 57 5.3 混合度及過剩面積之分析 59 5.4 單分子層的穩定性 67 5.5 壓縮係數及鬆弛行為 73 5.6 單分子層系統與微脂粒系統的關連性 75 結論 78 第六章 DSPC/paclitaxel混合系統 80 引言 80 結果與討論 82 6.1 表面壓-每分子佔據面積等溫線(□□A isotherm) 82 6.2 混合度及過剩面積之分析 84 6.3 單分子層的穩定性 89 6.4 壓縮係數及鬆弛行為 92 6.5 單分子層系統與微脂粒系統的關連性 94 結論 96 第七章 DSPC/Cholesterol/DSPE-PEG2000三成分 混合系統 97 引言 97 結果與討論 97 7.1 表面壓-每分子佔據面積等溫線(□□A isotherm) 98 7.2 混合度及過剩面積之分析 101 7.3 單分子層的穩定性 108 7.4 壓縮係數及鬆弛行為 111 7.5 單分子層與微脂粒系統的關連性 114 結論 114 第八章 DSPC/Cholesterol/DSPE-PEG2000/paclitaxel 四成分混合系統 117 引言 117 結果與討論 117 8.1 表面壓-每分子佔據面積等溫線(□□A isotherm) 117 8.2 混合度及過剩面積之分析 120 8.3 單分子層的穩定性 122 8.4 壓縮係數及鬆弛行為 124 8.5 討論 129 結論 130 第九章 總結 131 未來展望 132 參考文獻 133 附錄一: 著作 139 附錄二: 作者介紹 142

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