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研究生: 莊博荃
Po-Chuan Chuang
論文名稱: PLLA-PEG-PLLA 三團聯共聚物中氧化鋅奈米粒子在水溶液中共組裝之奈米尺寸現象
Nanoscale Size Phenomena of Co-assembly of Poly(L-lactic acid)- Poly(ethylene glycol)-Poly(L-lactic acid) Triblock Copolymers and Zinc Oxide in Aqueous Solutions
指導教授: 胡孝光
Hsiao-Kuang Hu
口試委員: 楊正昌
Cheng-Chang Yang
黃慶怡
Ching-Yi Huang
鄭詠馨
Yung-Hsin Cheng
學位類別: 碩士
Master
系所名稱: 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 70
中文關鍵詞: 三團聯共聚物氧化鋅奈米粒子共組裝
外文關鍵詞: Triblock copolymers, zinc oxide nanoparticles, co-assembly
相關次數: 點閱:208下載:3
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  • 本研究使用聚乙二醇與左旋-丙交酯以開環聚合法合成聚乳酸-聚乙二醇-聚乳酸(poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide))(PLLA-PEG-PLLA)三團聯共聚物。將共聚物的親水鏈段PEG聚合度固定為91,再利用凝膠滲透層析儀(GPC)對共聚物進行分子量的分析,計算出疏水段PLLA聚合度為74、103和132。
    以螢光探針法測量共聚物水溶液之臨界微胞濃度,可以觀察到疏水鏈段聚合度越大時,其臨界微胞濃度越小,越易形成微胞。將三團聯共聚物和不同粒徑之氧化鋅奈米粒子利用共沉澱法於水溶液中共組裝後,發現其臨界微胞濃度減少,代表氧化鋅奈米粒子和共聚物共組裝形成微胞時,奈米粒子增加了微胞的熱力學親和力,使微胞之疏水性增加,而隨著所包覆奈米粒子粒徑減少,其增加疏水性的效果更為明顯。再由共聚物水溶液之臨界微胞濃度計算微胞化自由能,發現當疏水鏈段長度越大時,其微胞化自由能之絕對值越大,代表疏水鏈段長度增加時,其微胞化之驅動力較大,較易形成微胞。而加入氧化鋅奈米粒子則能增加微胞化之驅動力,使微胞更易形成,且所包覆奈米粒子粒徑越小,此效果越明顯。
    以動態光散射儀測量微胞在水溶液中之平均粒徑,發現共聚物的疏水鏈段聚合度越大時,測得微胞在水溶液中的平均粒徑也越大,而包覆之氧化鋅奈米粒子粒徑越大時,微胞平均粒徑也越大。由於氧化鋅奈米粒子結構存在缺陷而帶正電,所以兩奈米粒子間有斥力產生,而奈米粒子粒徑越大,粒子間的斥力越大,導致微胞平均粒徑上升。
    利用熱重量分析徑儀測量氧化鋅奈米粒子在微胞疏水核中之重量百分率,探討奈米粒子粒對包覆平衡常數、分配自由能之影響。
    實驗結果發現當所包覆之氧化鋅奈米粒子和PLLA-PEG-PLLA三團聯共聚物共組裝時,隨著微胞包覆之奈米粒子粒徑越大,平衡常數、分配自由能(負值)之絕對值變大,即所包覆奈米粒子粒徑越大,奈米粒子從水溶液中進入微胞疏水核中之驅動力越大。
    為探討微胞包覆奈米粒子和藥物之包覆平衡常數和分配自由能的關係,本實驗以紫外/可見光分光光度計測定Vitamin K3於殘液之吸光光譜,利用檢量線得到未包覆藥物時的殘液濃度,計算藥物包覆平衡常數和分配自由能,實驗結果發現Vitamin K3之平衡常數、分配自由能(負值)之絕對值皆較氧化鋅奈米粒子小。
    研究發現微胞粒徑和奈米粒子粒徑皆會對共聚物水溶液之臨界微胞濃度、微胞在水溶液中之平均粒徑、平衡常數、分配自由能造成影響,而其中微胞粒徑所造成之影響較明顯。


    In this experiment, polyethylene glycol and L-lactide are used to synthesize poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) by ring-opening polymerization. The degree of polymerizations of the hydrophilic segment PEG in the copolymers are controlled to 91. The molecular weights of the copolymers are measured by gel permeation chromatography (GPC) and the degrees of polymerizations of the hydrophobic segment PLLA are calculated to be 74, 103 and 132.
    The critical micelle concentrations of the copolymers in aqueous solutions are measured by fluorescent probe method. It can be observed that the greater the degree of polymerization of the hydrophobic segment, the smaller the critical micelle concentration and the easier the formation of micelles. We co-assemble triblock copolymers and different sizes of zinc oxide nanoparticles in aqueous solutions by co-precipitation method. It is found that the critical micelle concentration decrease with the addition of particles. It means that when zinc oxide nanoparticles and copolymers are co-assembled to form micelles, the nanoparticles increase the thermodynamic affinity between micelle cores and water. As the sizes of the nanoparticles incorporated within micelles decrease, the effect of increasing the hydrophobicity becomes more obvious.
    The average sizes of the micelles in the aqueous solutions are measured by dynamic light scattering. It is found that the larger the degrees of polymerization of the hydrophobic segments, the larger the average sizes of the micelles. And the larger the particle sizes of zinc oxide nanoparticles incorporated within micelles, the larger the average sizes of the micelles. Because zinc oxide nanoparticle has defects in its structure, it is positively charged. There are the repulsive forces between two nanoparticles. The larger the sizes of the nanoparticles, the greater the repulsive forces between the particles, resulting in an increase in sizes of the micelles.
    The weight percentages of zinc oxide nanoparticles in the hydrophobic core of the micelles are measured by thermogravimetric analysis, and we explore the influence of the nanoparticle size on the particle loading equilibrium constant and the free energy of partition. The experimental results show that when zinc oxide nanoparticles and PLLA-PEG-PLLA tripolymer are co-assembled,and the sizes of the nanoparticles incorporated within micelles increases, the equilibrium constants and the absolute free energy of partition becomes larger. That is, the larger the sizes of the nanoparticles, the greater the driving force for the nanoparticles to enter the hydrophobic cores of the micelles.
    In order to explore the relationship between the loading equilibrium constants and the free energy of partition of the micelle loaded with nanoparticles and drug. The absorption spectrums of Vitamin K3 in the residual liquid are measured by UV/visible spectroscopy. Using the calibration curve to obtain the concentrations of the loaded drug. The loading equilibrium constant and the free energy of partition of drug can be calculated. The experimental results show that the values of the equilibrium constants and absolute free energy of partition of Vitamin K3 are smaller than those of zinc oxide nanoparticles.
    It is found that both the sizes of the micelles and the sizes of the nanoparticles will affect the critical micelle concentrations of the copolymers, average sizes of the micelles, equilibrium constants, and the free energy of partition. In comparison of two factors, the influence caused by the sizes of the micelles is more obvious.

    中文摘要………………………………………………………………..Ⅰ 英文摘要………………………………………………………………..Ⅲ 致謝……………………………………………………………………..Ⅶ 目錄..........................................................................................................Ⅷ 圖表索引………………………………………………………………..Ⅸ 前言………………………………………………………………..1 實驗方法…………………………………………………………..7 2.1 PLLA-PEG-PLLA三團聯共聚物之製備……………...………7 2.2 凝膠滲透層析儀分析………………………………………….8 2.3測量水溶液中臨界微胞濃度…………………………………..9 2.3.1配製待測臨界微胞濃度之共聚物溶液…………………...9 2.3.2螢光光譜測量臨界微胞濃度………………………….....10 2.4測量水溶液中微胞粒徑………………………………………10 2.4.1配製待測微胞粒徑之共聚物溶液……………………….10 2.4.2動態光散射儀測量微胞粒徑…………………………….11 2.5測量微胞中奈米粒子含量……………………………………12 2.5.1配製待測樣品…………………………………………….12 2.5.2熱重量分析儀測量…………………………………….…12 2.6 高分子微胞藥物包覆實驗…………………………………...13 2.6.1Vitamin K3 溶液之標定………………………………….13 2.6.2測量微胞中Vitamin K3含量……………………………13 三、結果與討論………………………………………………………..14 3.1 PLLA-PEG-PLLA三團聯共聚物之聚合與組成分析……….14 3.2 PLLA-PEG-PLLA三團聯聚合物之臨界微胞濃度………….15 3.2.1臨界微胞濃度之測量……………………………………..15 3.2.2臨界微胞濃度與疏水鏈段聚合度之關係………………..17 3.2.3加入氧化鋅奈米粒子對三團聯共聚物溶液臨界微胞濃度之影響………………………………………………..……...…..18 3.2.4含氧化鋅奈米粒子三團聯共聚物的微胞化……………..18 3.2.4.a 三團聯共聚物微胞化理論……………………………18 3.2.4.b氧化鋅奈米粒子粒徑變化對三團聯共聚物疏水鏈段與水的Flory-Huggins交互作用參數之影響…………………...23 3.2.5微胞化自能………………………………………………..23 3.3 PLLA-PEG-PLLA三團聯共聚物之微胞粒徑………………..25 3.3.1微胞粒徑與疏水鏈段聚合度之關係……………………..25 3.3.2加入氧化鋅奈米粒子對三團聯共聚物微胞粒徑之影響..26 3.3.3奈米粒子粒徑和共聚物微胞大小對CMC的影響……...28 3.4氧化鋅奈米粒子在共聚物中的組裝………………………….29 3.4.1氧化鋅奈米粒子在共聚物中所佔的含量………………..29 3.4.2氧化鋅奈米粒子在共聚物微胞中和水溶液中之濃度…..30 3.4.3利用粒子在微胞中和水溶液中的濃度測量平衡常數和分配自由能………………………………………………………...33 3.4.4奈米粒子粒徑和共聚物微胞大小對微胞中的分配自由能的影響…………………………………………………………...34 3.5 Vitamin K3於共聚物微胞中的分配…………………………...35 3.5.1 Vitamin K3在水溶液和共聚物微胞中之分配自由能…....35 3.5.2 Vitamin K3分子之直徑估算..……………………………..36 3.5.3分配自由能和Vitamin K3分子與氧化鋅粒子大小的關係 ……………………………………………………………………...37 四、結論………………………………………………………………..38 五、參考文獻…………………………………………………………..41

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