博碩士論文 104827605 詳細資訊




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姓名 阮宏南(Nguyen Hoang Nam)  查詢紙本館藏   畢業系所 生醫科學與工程學系
論文名稱 新型兩性磷脂類高分子聚合物與其自組裝奈米結構
(Self-Assembled Nanostructures of Novel Amphiphilic CP Polymer)
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摘要(中) 囊泡聚合物由於其在生物醫學與工業上的廣泛應用具有高穩定性,良好的生物相容性,以及作為不溶水藥物之奈米載體的能力,已然成為一個具吸引力的研究領域。因此,新型的自組裝奈米結構-可逆之膽鹼磷酸鹽(CP)的兩親兩性離子聚合物將在本研究中被陳述。首先,2-ethyl n-octyl phosphate (MOP)的合成是根據我們之前的研究,並且透過可逆加成-斷裂鏈轉移聚合反應聚合形成高分子。根據溶劑、添加劑以及製備方法的不同,聚合物可以自組裝成各種聚合物囊泡。再來運用幾種技術來確認pMOP囊泡的結構,包括動態光散射(DLS),原子力顯微鏡(AFM)和低溫電子顯微鏡(Cryo-TEM)。接下來運用螢光光譜得到單體和聚合物的臨界微胞濃度(CMC),並與現有的表面活性劑相比,顯示出極低的CMC。之後透過Cryo-TEM圖像證實了pMOP囊泡的可控尺寸和形態,其中膜厚度幾乎與磷脂雙分子層相同。這種兩性離子聚合物具有模仿生物膜的巨大潛力以及與許多生物分子結合的能力,當在對奈米結構的製造具精細控制成功時,將在生物醫學領域開拓廣泛的應用。
摘要(英) Polymer vesicles have been an attractive research field due to their wide range of application in both biomedical and industrial with the good properties such as high stability, good biocompatibility, the ability as a nanocarrier of the water-insoluble drug, etc. Herein, the self-assembly nanostructure of a new reverse choline phosphate (CP) amphiphilic zwitterionic polymer is reported. 2-ethyl n-octyl phosphate (MOP) was synthesis based on our previous work and polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer can self-assembly into various kinds of polymer vesicles depending on the solvent, additives and the preparation method. Several techniques were used to confirm the structure of pMOP vesicles including Dynamic light scattering (DLS), Atomic Force Microscopy (AFM) and Cryo-electron microscopy (Cryo-TEM). The critical micelle concentration (CMC) of the monomer and polymer were obtained by using fluorescence spectroscopy, which showed an extremely low CMC compared to the available surfactants. The controllable size and morphologies of pMOP vesicles were demonstrated by Cryo-TEM images, in which the membrane thickness is nearly equal to the phospholipid bilayer. With a very high potential of mimicking the biological membranes and the ability to incorporate with many biomolecules, when achieving finely controlling the nanostructure fabrication, this zwitterionic polymer will open a wide range of applications in biomedical field.
關鍵字(中) ★ 奈米結構
★ 兩性離子聚合物
★ 自組裝
★ 囊泡
關鍵字(英) ★ nanostructure
★ zwitterionic polymer
★ self-assembly
★ vesicle
論文目次 TABLE OF CONTENTS VI
LIST OF FIGURES VIII
LIST OF TABLES XI
LIST OF ABBREVIATIONS XII
ABSTRACT XIII
CHINESE ABSTRACT XIV
ACKNOWLEDGMENT XV
CHAPTER 1: LITERATURE REVIEW 16
1.1. Introduction 16
1.2. Cell membrane structure 17
1.3. Polyzwitterions 19
1.3.1. Poly(sulfobetaine) 20
1.3.2. Poly(carboxybetaine) 20
1.3.3. Poly(phosphorylcholine) 20
1.3.3.1. Synthesis of PC-based materials 21
1.3.3.2. Inverted Choline Phosphate (CP) 22
1.4. Radical Polymerization 24
1.4.1. Mechanism of RAFT 26
1.4.2. Structure of RAFT agents 28
1.4.3. Classes of chain-transfer agents (CTA) 29
1.4.4. Compatibility of RAFT agents with different monomers 30
1.4.5. Choice of initiator 30
1.5. Polymer vesicles preparation method 31
1.5.1. Solvent-switch method 33
1.5.2. Solvent-free methods 33
1.5.2.1. Rehydration method 34
1.5.2.2. pH tuning in pure water 36
1.5.2.3. Polyion complex vesicles (PICsomes) 36
1.5.3. Polymerization-induced self-assembly: PISA 37
1.5.4. Centrifugation-induced self-assembly 39
1.5.5. Microfluid method 40
1.5.6. Nanoprinting method 41
CHAPTER 3: MATERIALS AND METHODS 45
3.1. Materials 45
3.2. Methods 45
3.2.1. Preparation of OOP 45
3.2.2. Preparation of MOP 46
3.2.4. CMC determination 46
3.2.5. Preparation of different nanostructures 47
3.3. Characterization 48
CHAPTER 4: RESULTS AND DISCUSSION 50
4.1. Synthesis of pMOP 50
4.2. Characterization of pMOP 54
4.3 CMC determination of MOP and pMOP 55
4.4. Polymer vesicle size study by DLS 58
4.4.1. Comparison of pMOP with different molecular weight 58
4.4.2. pMOP in the solution with and without FBS 59
4.4.3. pMOP incorporating with Cholesterol 61
4.5.1. Cryo-TEM and AFM images of pMOP – Curcumin nanostructure 62
4.5.2. Nanostructure of pMOP in other conditions 66
4.5.2.1. pMOP in water: Hexane (99:1) 66
4.5.2.2. pMOP – Curcumin in THF 67
4.5.2.3. pMOP incorporate with Cholesterol in water 68
CHAPTER 5: CONCLUSIONS AND FUTURE WORKS 70
REFERENCES 71

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指導教授 黃俊仁(Chun-Jen Huang) 審核日期 2018-1-29
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