馬倫哥尼效應(Marangoni effect)為在流體界面上因為表面張力梯度差所引發的流體流動的現象，表面張力較高的液體會將表面張力較低的液體拉過來，藉此來平衡整個界面張力。由於馬倫哥尼效應快速和簡易的特性，使其被廣泛的應用於各種工程研究領域上。本研究利用馬倫哥尼效應研發了一快速且簡易的方法來製備具有相轉換性質的微米粒子，並將此製備的微米粒子應用於口服親脂藥物投遞。研究裡，我們將可以改變表面張力的乙醇、具有相轉換性質的脂肪酸十二烷酸(dodecanoic acid)和親脂藥物維他命D3混和。混合後的液體滴到水溶液的表面上後，會因為乙醇低表面張力的性質，使得十二烷酸和維他命D3快速地分散於溶液中，形成微米大小的小油珠。組成的小油珠會因十二烷酸相轉換的特性而逐漸冷卻，固化形成包覆有維他命D3的微米粒子。我們藉由改變界面活性劑、載藥量、乙醇濃度、水溶液酸鹼值及環境溫度，來最佳化微米粒子的製備方法。在體外實驗裡，我們利用高速攝影機觀察液體利用馬倫哥尼效應快速分散成小油珠的情形。在動物實驗裡，我們分別餵食老鼠維他命D3以及包覆維他命D3的微米粒子。實驗結果發現，餵食包覆維他命D3的微米粒子能夠有效的增加此藥物的口服生物可利用率。本研究的結果證實，我們成功的開發了ㄧ利用馬倫哥尼效應製備的相轉換微米粒子，並能夠應用於口服親脂藥物的投遞。

Marangoni effect is the mass transfer phenomenon between two phases owing to a gradient of the surface tension. Marangoni flow can be driven from a region of lower surface tension to a region of higher surface tension. In this study, a fast and facile platform for fabricating phase-change materials-based microparticles by Marangoni effect for lipophilic drugs delivery is developed. With a huge difference in surface tension between ethanol and water, a drop of ethanol solution of dodecanoic acid and lipophilic drug (vitamin D3) can rapidly spread and spontaneously breaks up into several micro-scale oil droplets. As the local temperature slowly decline, the oil droplets release their stored heat energy and solidify to form vitamin D3-encapsulated microparticles. The phase-change materials-based microparticles were prepared and optimized with different amount of surfactant, drug dose, ethanol, pH, and temperature. In the in vitro study, a high-speed camera was used to record the rapid spreading process of the prepared solution. The results of the In vivo study indicated that rats that were orally administered with vitamin D3-encapsulated microparticles had a higher bioavailability than those that was orally administered with free form vitamin D3. This study provides a novel approach for the preparation of microparticles and can be applicable to other systems toward versatile materials with specific properties and functions.

摘要 Ⅰ
目錄 III
圖錄 V
一、緒論 1
1.1 口服投遞藥物 1
1.2 脂肪酸(Fatty acid) 2
1.3 馬倫哥尼效應(Marangoni effect) 2
1.4 相轉換(Phase change) 6
1.5 吐溫20(Tween 20) 6
1.6 維他命D3(Vitamin D3) 7
1.7 研究動機與實驗目的 8
1.8 實驗架構 10
二、材料與方法 11
2.1 材料 11
2.2 微米粒子製備 11
2.3 油相之分析 11
2.3.1 維他命D3藥量分析 11
2.3.2 乙醇濃度分析 11
2.4 水相之分析 12
2.4.1 界面活性劑之濃度 12
2.4.2 水相溫度 12
2.4.3 水相酸鹼值 12
2.4.4 微米粒子包覆度(loading content)及包覆效率(loading efficiency) 13
2.5 高速攝影機拍攝馬倫哥尼效應 13
2.6 藥物洩漏分析(drug leakage) 13
2.7 動物血漿內維他命D3濃度 14
三、結果與討論 15
3.1 油相之分析 15
3.1.1 維他命D3藥量分析 15
3.1.2 乙醇濃度分析 16
3.2 水相之分析 16
3.2.1 界面活性劑之濃度 16
3.2.2 水相溫度 19
3.2.3 水相酸鹼值 21
3.3 高速攝影機拍攝馬倫哥尼效應 22
3.4 藥物洩漏分析(drug leakage) 23
3.5 動物血漿內維他命D3濃度 24
四、結論 26
五、參考文獻 27

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