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研究生:黃筠喬
研究生(外文):Yun-Chiao Huang
論文名稱:利用硬酯醇改質葡萄聚醣製備高分子液胞及 其結構探討
論文名稱(外文):Polymer Vesicles Self-Assembling from Octadecanol Modified Dextrans in Aqueous Solutions
指導教授:邱信程
指導教授(外文):Hsin-Cheng Chiu
口試委員:蔡毓楨陳崇賢
口試委員(外文):Yu-Chen TsaiChorng-Shyan Chern
口試日期:2009-07-14
學位類別:碩士
校院名稱:國立中興大學
系所名稱:化學工程學系所
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:91
中文關鍵詞:高分子液胞溶劑置換法葡萄聚醣雙性高分子二次乳化法二階段二次乳化法複合型高分子液胞
外文關鍵詞:dextranamphiphilic copolymerspolymeric vesiclessolvent replacementdouble emulsionmultivesicle
相關次數:
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  • 點閱點閱:13
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在研究中,利用硬酯醇(Octadecanol)改質葡萄聚糖(dextran),並以二種製備方法製備高分子液胞。實驗中利用轉酯化反應將已活化的硬酯醇(18OH-CI) 成功改質葡萄聚醣鏈段得葡萄聚醣- 硬酯醇
dextran-g-octadecanol(DO)高分子,且利用核磁共振氫譜儀及紅外線光譜儀鑑定改質率。藉由調控硬酯醇的進料比,分別製備不同硬酯醇的碳鏈接枝比例(10、20、30 及40 mol %)之雙性高分子,其改質效率達九成。
利用溶劑置換法搭配不同初始水量的添加,可得不同尺寸大小之高分子液胞,以1H NMR、DLS 及TEM 分析於不同DMSO/H2O 比例下雙性高分子排列情形,當水加入高分子DMSO 溶液時,雙性高分子的烷鏈C18 鏈段因溶解度的降低進而因疏水作用趨使高分子以水為核心形成高分子液胞,且雙性高分子於臨界水含量(Critical water content,CWC)之後開始形成穩定高分子液胞結構,液胞粒徑大小不因進一步的溶劑置換而有所變化。由SLS 分析可知不同H2O 添加比例下,所形成的結構皆為高分子液胞,即Rg/Rh 比值趨近於1。此外,TEM 實驗中亦證實奈米高分子液胞內部可包覆水溶性螢光物calcein。
另一方面,採用二次乳化法製備微米高分子液胞(ca.1-27μm),結果指出,當DMSO 所佔比例上升會降低乳化液滴之界面張力而使液胞粒徑下降,而提高內部水相的W1 離子強度可穩定乳化液滴有助於液胞之形成,另外因滲透壓的提升而使液胞粒徑明顯增加。另於螢光物質包覆實驗中,可知小分子可穿透高分子液胞的胞膜,而較大分子量之物質則可包覆於液胞內部水相中。最後利用二階段二次乳化法,成功製備出複合型高分子液胞以非同心圓方式同時包覆數個尺寸較小高分子液胞於一較大尺寸液胞的內部水相中,藉提升高分子液胞於藥物釋放控制應用。
In this work, the biodegradable amphiphilic dextran-based copolymers comprising of different octadecanol contents are obtained by partial transesterification of activated
octadecanol with dextran segments. The chemical compositions of copolymers are determined exactly by 1H-NMR and FT-IR measurements. A series of copolymers is
utilized further to prepare polymeric vesicles by two approaches.
These nano-scale polymeric assemblies are attained by self-assembly of amphiphilic copolymers in DMSO/H2O co-solvents and then dialysis against water.
Combining the results of 1H-NMR and dynamic light scattering (DLS) measurements,the polymeric assemblies can be controlled well by adjusting the DMSO/H2O ratio used
during self-assembly of copolymers. Importantly, the Rg/Rh ratios of the above polymeric assemblies examined by static light scattering (SLS) are approximately 1.0,confirming strongly that the structure of assemblies is presented in vesicle-like form.Moreover, the transmission electron microscopy (TEM) images show that thehydrophilic calcein molecules can be confined within the interior aqueous compartment of polymeric vesicles.
On the other hand, the micro-scale polymeric vesicles with ca. 1~27μm in size can be obtained by double emulsion (W1/O/W2) process. Increasing the DMSO content of the DMSO/CHCl3 co-solvent reduces the vesicle size .Furthermore, elevating the ionic concentration in the W1 phase not only stabilizes efficiently the vesicle structure but also enlarges the vesicle size. From the data of fluorescence experiments, the small calcein probes can freely transport across the vesicular membrane, whereas the large FITC-dextran (Mw 4000 or 10000 g/mol) molecules within the aqueous compartment of vesicles are incapable of diffusing into outside aqueous phase. For expanding the
applications of polymeric vesicles in drug delivery system, the multivesicle assemblies can be obtained further by suspending small vesicles (prepared in the first stage) in the W1 phase of the second-stage double emulsion process that was used to produce large vesicles.
目錄
第一章、緒論.............................................. 1
第二章、 文獻回顧......................................... 2
2-1 微脂粒介紹............................................ 2
2-2 高分子液胞(polymeric vesicles or polymersomes)........ 3
2-3 液胞之種類............................................ 5
2-4 雙性分子親水鏈段重量分率(f)對聚集形成形態的影響....... 6
2-5 天然高分子葡萄聚醣(dextran) .......................... 9
2-5-1 葡萄聚醣(dextran)簡介:............................. 9
2-5-2 改質葡萄聚醣及其應用............................... 10
第三章、實驗..............................................12
3-1 實驗藥品............................................. 12
3-2 實驗儀器............................................. 13
3-3 實驗原理............................................. 14
3-3-1 螢光分析........................................... 14
3-3-1-1 焦油腦 Pyrene ................................... 14
3-3-1-2 鈣黃綠素(Calcein) ............................... 15
3-3-1-3 尼羅紅(Nil red) ................................. 15
3-3-2 二次乳化法(W1/O/W2 double emulsion method) ........ 16
3-3-3 光散射分析......................................... 17
3-3-3-1 光散射簡介....................................... 17
3-3-3-2 動態光散射粒徑分析儀Dynamic Light Scattering (DLS)18
3-3-3-3 靜態光散射儀Static Light Scattering (SLS)........ 19
3-3-4 螢光光譜儀(Spectorfluorophotometer)................ 21
3-3-5 穿透式電子顯微鏡................................... 21
3-3-6 場發射掃描式電子顯微鏡............................. 22
3-3-7 共軛聚焦雷射掃描顯微鏡............................. 22
3-3-8 光學顯微鏡......................................... 22
3-3-9 微分干涉差顯微鏡................................... 23
3-4 實驗方法............................................. 24
3-4-1 硬酯醇改質葡萄聚醣高分子合成及性質分析............. 24
3-4-1-1 硬酯醇(Octadecanol)之活化........................ 24
3-4-1-2 葡萄聚醣(Dextran)接枝Octadecanol-CI 之反應........25
3-4-2 高分子液胞之製備................................... 26
3-4-2-1 以溶劑置換法製備高分子液胞....................... 26
3-4-2-2 以二次乳化法製備高分子液胞....................... 27
3-4-3 利用核磁共振氫譜儀定量接枝高分子................... 28
3-4-4 動態光散射粒徑分析儀之高分子液胞結構分析........... 28
3-4-5 靜態光散射儀對高分子液胞結構之分析................. 28
3-4-6 高分子液胞之臨界聚集濃度分析....................... 29
3-4-7 穿透式電子顯微鏡之高分子液胞結構之分析............. 29
第四章、結果與討論....................................... 30
4-1 硬酯醇改質葡萄聚醣雙性高分子之組成鑑定............... 30
4-2-1 奈米高分子液胞結構探討............................. 33
4-2-1-1 雙性高分子之臨界聚集濃度測量..................... 33
4-2-1-2 添加初始水量對高分子溶液之1H-NMR 核磁共振儀分析. .37
4-2-1-3 添加初始水量對高分子自組裝行為之影響............. 41
4-2-1-4 溶劑置換後之高分子液胞之型態分析................. 45
4-2-1-5 利用SLS 分析高分子液胞型態....................... 48
4-2-1-6 利用電子顯微鏡觀察高分子液胞型態................. 51
4-2-1-7 包覆水溶性螢光物之高分子液胞..................... 56
4-2-2 微米高分子液胞結構探討............................. 59
4-2-2-1 利用共軛聚焦螢光顯微鏡觀高分子液胞分析........... 60
4-2-2-2 微米高分子液胞之包覆實驗......................... 63
4-2-3 高分子液胞於溶劑置換法之形成機制................... 65
4-3 利用二次乳化法製備高分子液胞......................... 66
4-3-1 以油相組成調控高分子液胞(內部水相為純水)粒徑....... 66
4-3-2 不同離子強度調控高分子液胞......................... 71
4-3-3 高分子液胞包覆水溶性螢光物質之效率評估............. 73
4-3-4 離子強度對不同油相組成調控高分子液胞粒徑........... 76
4-3-5 複合型高分子液胞................................... 80
第五章 結論.............................................. 86
第六章 參考文獻.......................................... 87
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