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研究生:林芳羽
研究生(外文):Fang-Yu Lin
論文名稱:溶劑退火方式製備高裝載性嵌段高分子奈米膠囊與其控制釋放
論文名稱(外文):Polymersomes with high loading capacity prepared by solvent annealing method and their controlled release behaviors
指導教授:童世煌
指導教授(外文):Shih-Huang Tung
口試委員:邱文英戴子安劉定宇
口試委員(外文):Wen-Yen ChiuChi-An DaTing-Yu Liu
口試日期:2014-07-17
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:高分子科學與工程學研究所
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:2014
畢業學年度:102
語文別:中文
論文頁數:89
中文關鍵詞:雙親性團聯式共聚物自組裝液胞阿斯匹靈
外文關鍵詞:Amphiphilic block copolymersSelf-assemblyVesiclesAspirin
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雙親性團聯式共聚物可以於選擇性溶劑形成自組裝結構,其中喜好溶劑的鏈段傾向和溶劑接觸,而不喜好溶劑的鏈段被屏蔽遠離溶劑,不同於傳統製備液胞方法,我們發現團聯式共聚物PS-b-PAA、PS-b-PEO和PCL-b-PEO可以藉由溶劑退火的方式在藥物分子阿斯匹靈中自組裝形成液胞,當添加團聯式共聚物於大量阿斯匹靈中,阿斯匹靈會與共聚物的其中一嵌段結合,猶如選擇性溶劑膨潤該嵌段,使體積分率改變,形成雙層結構,於溶劑退火的過程中,滲入的溶劑賦予團聯式共聚物和阿斯匹靈移動力,使雙層結構能夠環起來形成內外皆充滿阿斯匹靈的液胞。此溶劑退火的方式,可以避免傳統高溫熱退火製備液胞時,造成藥物分子發生不必要的化學反應,當我們以穿透式電子顯微鏡觀察經由適當溶劑所萃取的液胞結構,發現該液胞結構具有充滿藥物的核心,藥物承載的能力高達59±5%,遠高於溶液系統中所形成的傳統液胞結構藥物承載能力約30-40%。我們也測試了包覆阿斯匹靈液胞的釋放行為,發現PS-b-PAA液胞可經由控制將阿斯匹靈釋放出來,在水溶液中加入不同比例的dioxane,因dioxane可膨潤PS和PAA鏈段,能增加液胞穿透度,促使阿斯匹靈釋放,此外,我們也觀察液胞在不同pH值溶液下的釋放行為,發現藥物的累積釋放量明顯受pH值影響。

It is well known that amphiphilic block copolymers in selective solvents can form self-assembled structures, where solvophilic blocks tend to contact with solvents while solvophobic blocks are shielded from the solvents. Different from the conventional preparation of vesicles in liquid systems, we found that block copolymers, including poly(styrene-b-acrylic acid) (PS-b-PAA), poly(styrene-b-ethylene oxide) (PS-b-PEO), and poly(caprolactone-b-ethylene oxide) (PCL-b-PEO), can directly self-assemble into vesicles in aspirin, a drug molecule, by solvent annealing. When mixing the block copolymers in a great amount of aspirin, aspirin works as “selective solvent” that associates with one of the blocks and swells the block, thus changing the volume fraction of the blocks, which firstly leads to the formation of bilayer structures. During following solvent annealing, the penetrated solvent molecules impart mobility to block copolymers and aspirin. The bilayers are then wrapped into vesicles with aspirin filled in both interior and exterior. The advantage of solvent annealing method is that it prevents unnecessary chemical reactions of drug molecules that may be caused by conventional thermal annealing method at high temperature. The vesicular structures after extracting by appropriate solvents were probed by transmission electron microscopy (TEM). The extracted vesicles are filled with aspirin in the core and the drug loading content can reach as high as 59±5%, which is much higher than that of conventional vesicles formed in liquid systems (~30-40%). We have tested the release behaviors of the aspirin-loaded vesicles. Aspirin can be released in a controlled manner from PS-b-PAA vesicles in aqueous solutions with different concentrations of n-dioxane, a good solvent to both PS and PAA blocks. We also examined the effect of pH values on the release behaviors of the aspirin-loaded vesicles in aqueous solutions. The cumulative release of aspirin was found to be strongly pH-dependent.

誌謝 I
Abstract II
摘要 IV
Table of contents V
List of figure VII
Chapter 1 Introduction 1
1-1 Background 1
1-2 Motivation and Objectives 3
Chapter 2 Theory and Literature Review 5
2-1 Block copolymer and supramolecules 5
2-1.1 Block copolymer 5
2-1.2 Supramolecules 10
2-2 Amphiphilic block copolymers micellar solution 17
2-3 Blend of diblock copolymer 24
2-3.1 Block copolymer self-assembled in homopolymer 24
2-3.2 Block copolymer self-assembled in small molecule 27
2-4 Polymersomes for drug release 30
Chapter 3 Experimental Section 34
3-1 Materials 34
3-2 Experimental methods 38
3-2.1 Preparation of bulks 38
3-2.2 Annealing procedure 38
3-2.3 Ultrathin session 38
3-2.4 Extraction of self-assembled structures 39
3-2.5 Drug release 39
3-3 Characterization 42
Chapter 4 Results and Discussion 44
4-1 The interaction between PS-b-PAA and aspirin 44
4-2 Preparing vesicles from amphiphilic block copolymers by solvent annealing 52
4-2.1 Aspirin-loaded vesicles of PS(42000)-b-PAA(4500) 52
4-2.2 Aspirin-loaded vesicles formed by PS-b-PAA with different molecular weight 62
4-2.3 Aspirin-loaded vesicles formed from other block copolymers 68
4-3 Release of aspirin from polymersomes 72
4-3.1 Aspirin released from vesicles in n-dioxane/water mixtures 73
4-3.2 Aspirin released at different pH values 77
Chapter 5 Conclusions 83
Reference 84


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