邱文英臺灣大學：材料科學與工程學研究所林佳龍Lin, Chia-LungChia-LungLin2007-11-262018-06-282007-11-262018-06-282005http://ntur.lib.ntu.edu.tw//handle/246246/55149本研究目的在於製備以聚(氮-異丙基丙烯醯胺)為主體衍生之次微米級溫度感應型共聚微膠體，並探討其性質及應用。內容共分為三大部分。 第一部份包含第二、三、四章。第二章中探討溫度感應型共聚微膠體的製備與溫度感應性質。首先以多種方法製備出不同粒徑大小的微膠體。接著以無乳化劑乳化聚合法為主合成粒徑約200~500 nm之共聚微膠體，討論共聚單體的種類及組成對於合成機構、反應速率、粒徑、顆粒型態及其溫度感應性質的影響。第三章主要以熱力學模型來探討聚(氮-異丙基丙烯醯胺)與聚(氮-異丙基丙烯醯胺-共聚-丙烯酸)微膠體之溫度感應型澎潤行為。模型中以具少量參數之代數方程式描述微膠體之溫度感應型澎潤行為之實驗結果，並釐清高分子-水分子作用力、交聯作用與官能基解離對於此溫度感應型澎潤行為的貢獻及影響。第四章則以聚(氮-異丙基丙烯醯胺-共聚-丙烯酸)微膠體之特性應用於製備溫度及濕度感應之具導電性複合微膠體，發現此複合顆粒受合成機構、顆粒之型態與結構影響，在不同溫度及濕度下具有不同之導電性質。 第二部份包含第五、六、七章。第五章利用在聚(丙烯酸)寡聚物存在下以共沈澱法合成水相穩定之磁性流體，討論其合成機構、結構及性質。發現此具奈米四氧化三鐵顆粒之磁性流體具備超順磁性且其於水相中之穩定性可由溶液之酸鹼性控制。第六章則利用此磁性流體與氮-異丙基丙烯醯胺及甲基丙烯酸單體合成同時具溫度感應性及超順磁性之交聯水膠。討論單體、交聯劑的比例與濃度對於其性質與溫度感應型澎潤行為的影響，建立組成、結構、性質三者間的關係。接著於第七章中，以W/O 迷你乳化聚合法，利用環己烷為連續油相，而含磁性流體之單體液滴分散相為微小反應場所，製備奈米四氧化三鐵均勻包覆其中之溫度感應型超順磁性複合乳膠顆粒。討論組成對於反應、熱性質、溫度感應性質及磁性性質的影響。 第三部份包含第八、九章。主要以無乳化劑乳化聚合法製備具溫度感應性核殼型共聚乳膠顆粒，其中以聚(氮-異丙基丙烯醯胺-共聚-幾丁聚醣)為主構成核部分，而以聚(甲基丙烯酸-共聚-甲基丙烯酸甲酯)為主形成殼部分。第八章改變核部分之組成，第九章改變殼部分之組成，討論對於合成及性質之影響，同時討論不同組成及不同環境溫度下乳膠顆粒之藥物釋放行為與其蛋白質(ligand)鍵結能力，期望應用此乳膠顆粒於標靶性藥物載體。 本研究之原創性及成果貢獻在於： 1.首次利用穿透式電子顯微鏡觀察顆粒型態，配合反應動力分析與溫度感應澎潤行為之量測，深入地探討導入不同共聚單體對成核機制與性質的影響，成功的建構組成、成核機制、顆粒型態與溫度感應性質間的關係。 2.首次以兼具考慮高分子-水分子作用力、交聯作用與官能基解離作用的熱力學模型，成功地描述微膠體之溫度感應型澎潤行為，並釐清不同作用對表現性質的貢獻及影響。 3.首次利用聚(氮-異丙基丙烯醯胺-共聚-丙烯酸)微膠體的特殊型態結構與溫度感應性，成功製備溫度及濕度感應之具導電性複合微膠體。 4.首次以聚(丙烯酸)寡聚物以in-situ的方式合成含較小顆粒四氧化三鐵的水相穩定超順磁磁性流體。 5.首次以W/O 迷你乳化聚合法，利用pH值調整磁流穩定性與使用氧化還原型起始劑，成功製備均勻包覆奈米四氧化三鐵，且兼具溫度感應性及超順磁性之複合乳膠顆粒。 6.首次以氮-異丙基丙烯醯胺與幾丁聚醣，合成較小顆粒且兼具溫度感應與酸鹼感應之生物可分解性微膠體，並利用後續設計之核殼結構評估其應用於標靶性藥物載體之可行性。This research was divided into three parts to study the preparation, properties, and application of poly(N-isopropylacrylamide) related thermoresponsive copolymer microgels. In the first, the thermoresponsive copolymer latex particles with the average diameter of about 200~500nm were prepared via surfactant-free emulsion polymerization. The effects of co-monomers and composition on the synthesis mechanism, kinetics, particle size, morphology, and thermoresponsive properties of the copolymer latex were first studied to realize the relationship between the synthesis condition, the particle morphology and the thermoresponsive properties successfully. The LCST of the latex copolymerized with AA monomers was raised to higher temperature, the LCST of the latex copolymerized with SA monomers was not changed. A proposed model with a few adjustable model parameters, which first considered the contributions of mixing, elasticity and electrostatic effect, was established to represent swelling behavior of the poly(NIPAAm) homopolymer and poly(NIPAAm-co-AA) copolymer microgels. A good agreement between the experimental data and our proposed model was obtained. The polymerization of pyrrole in presence of poly(NIPAAm-co-AA) microgels resulted in a novel composite microgels filled with conducting polypyrrole inclusions. Such smart composite microgels exhibited temperature and humidity dependent electrical conductivity. And its structure was reorganized after the treatment of high temperature and humidity that resulted in an increase of conductivity. Secondarily, a stable ferrofluid containing Fe3O4 nanoparticles was synthesized via co-precipitation method in the presence of poly(acrylic acid) oligomer. The mechanism, microstructure and properties of the ferrofluid were investigated. This ferrofluid showed superparamagnetic property and could be dispersed in monomer solution stably by adjusting the pH value of solution. Then thermal-responsive poly(NIPAm-co-MAA) copolymer networks containing Fe3O4 nanoparticles was synthesized in the presence of ferrofluid. The effects of the mole ratio of MAA/NIPAAm, the concentrations of monomers and crosslinking agent, the addition of ammonium solution and the content of ferrofluid were discussed. The swelling and thermo-responsive behaviors of the complex polymer networks were also studied, and the composition-morphology-property relationship was established. As soon as this thermoresponsive magnetic hydrogel was prepared and characterized successfully, the thermoresponsive magnetic microgels were prepared in situ by using “W/O miniemulsion polymerization” since the monomer droplets with magnetic nanoparticles acted as ‘‘nanoreactors’’ in this process. This polymerization was proceeded in cyclohexane at room temperature with span80 as the emulsifier, and APS / SMBS were used as redox initiator system. Fe3O4 nanoparticles were homogeneously encapsulated inside the poly(NIPAAM-co-MAA) latex particles. The properties of the composite latex were examined by using DSC, TGA and FTIR. Finally, the superparamagnetic and thermoresponsive characteristics of this functional composite latex were also investigated. Finally, the synthesis, properties, and application of a thermal-sensitive core-shell copolymer latex were studied, where the crosslinked copolymer of N-isopropylacrylamide (NIPAAm) and chitosan was prepared as the core, and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. The core-shell copolymer latex was synthesized by soapless dispersion polymerization. The weight ratio of chitosan/NIPAAm and the concentration of crosslinking agent or the weight ratio of MAA/MMA and the concentration of shell monomers (MAA and MMA) in feed had been changed to investigate their effects on the particle size, reaction rate, zeta-potential, surface functional groups, and specific surface area of latex particles. The swelling and thermo-sensitive behavior of the film made from these core-shell latexes were also studied under different pH values of buffer solution. A series of experiments on the application of this latex on drug release were performed, and the potential of the latex being applied on targeting drug carrier was evaluated.Table of Contents I List of Tables VIII List of Figures IX 摘要 XVII Abstract XIX Chapter 1 Introduction 1 1.1. Introduction to Poly(NIPAAm) Microgels 1 1.2. Thermoresponsive Poly(NIPAAm)-based Copolymer Microgels 3 1.3. Thermoresponsive Superparamagnetic Copolymer Composite 4 1.4. Thermoresponsive Core-shell Copolymer Latex for the Targeting Drug Carrier Application 5 1.5. Reference 6 Chapter 2 Preparation, Morphology and Thermo-responsive Properties of poly(NIPAAm)-based Copolymer Microgels 8 Abstract 8 2.1. Introduction 9 2.2. Experiment 12 2.2.1. Material 12 2.2.2. Preparation of poly(NIPAAm) Microgels with Different Size 12 2.2.3. Preparation of poly(NIPAAm)-based Copolymer Microgels with Different Thermoresponsive Properties 13 2.2.4. Conversion 13 2.2.5. Morphology Observation of Microgels 14 2.2.6. Measurement of Swelling Behavior for Microgels 14 2.3. Results and Discussion 16 2.3.1. Preparation of poly(NIPAAm) Microgels with Different Size 16 2.3.1.1. Particle Size Larger than 500 nm (synthesized by solution polymerization at room temperature) 16 2.3.1.2. Particle Size Smaller than 200 nm (synthesized by emulsion polymerization) 16 2.3.1.3. Particle Size between 200 to 500 nm (synthesized by surfactant-free emulsion polymerization) 17 2.3.2. Preparation and Morphology of (NIPAAm-co-hydrophilic monomer) Microgels 17 2.3.2.1. Poly(NIPAAm) homopolymer Microgels 18 2.3.2.2. Effect of Acrylic Acid 19 2.3.2.3. Effect of Sodium Acrylate 19 2.3.3. Thermoresponsive Properties of (NIPAAm/hydrophilic monomer) Microgels 21 2.3.3.1. Particle Size Analysis 21 2.3.3.1.1. Effect of Acrylic acid 22 2.3.3.1.2. Effect of Sodium Acrylate 23 2.3.3.2. Cloud Point Analysis 24 2.3.3.2.1. Effect of Acrylic acid 24 2.3.3.3.2. Effect of Sodium Acrylate 24 2.4. Conclusion 26 2.5. Reference 27 Chapter 3 A Model for the Thermal Induced Volume Phase Transition of poly(NIPAAm) and poly(NIPAAm-co-AA) Microgels 29 Abstract 29 3.1. Introduction 30 3.2. Experiment 33 3.2.1. Material 33 3.2.2. Preparation of Microgels 33 3.2.3. Measurement of Swelling Behavior for Microgels 33 3.3. Theoretical Consideration 35 3.3.1. Swelling Equilibrium of Homopolymer Gel in the Solvent 35 3.3.1.1. Nonionic Gel 35 3.3.1.2. Ionic Gel 36 3.3.1.3. The Free Energy Contribution of Elasticity 36 3.3.1.4. The Free Energy Contribution of Mixing 37 3.3.1.5. The Free Energy Contribution of Electrostatic Interactions 38 3.3.2. Equilibrium Condition for Homopolymer Gel / Solvent System 39 3.3.3. Swelling Equilibrium of Copolymer Gel in the Solvent 42 3.3.4. Equilibrium Condition for Copolymer Gel / Solvent System 43 3.4. Results and Discussion 45 3.4.1. Swelling Behavior of poly(NIPAAm) microgels 45 3.4.1.1. Flocculation Effect 45 3.4.1.2. The Free Energy Contribution of Mixing 46 3.4.1.2.1. Polymer-Solvent Interaction Parameter 46 3.4.1.2.2. Effect of (parameters and ) 47 3.4.1.2.3. Effect of (parameter ) 47 3.4.1.3. The Free Energy Contribution of Elasticity 48 3.4.1.3.1. Effect of 48 3.4.1.3.2. Effect of 49 3.4.1.4. The Free Energy Contribution of Electrostatic Interactions 50 3.4.2. Swelling Behavior of poly(NIPAAm-co-AA) copolymer microgels 51 3.4.2.1. The Free Energy Contribution of Mixing 52 3.4.2.1.1. Polymer-Solvent Interaction Parameter 52 3.4.2.1.2. Temperature Dependent Interaction Parameter 53 3.4.2.1.3. Polymer Volume Fraction Dependent Interaction Parameter 54 3.4.2.2. The Free Energy Contribution of Elasticity 55 3.4.2.3. The Free Energy Contribution of Electrostatic Interactions 55 3.5. Conclusion 56 3.6. Reference 58 Chapter 4 Polypyrrole / poly(N-isopropylacrylamide-co-acrylic acid) Thermosensitive Electrically Conductive Composite Microgels 61 Abstract 61 4.1. Introduction 62 4.2. Experiment 64 4.2.1. Material 64 4.2.2. Preparation of poly(NIPAAm/AA) Copolymer Microgels 64 4.2.3. Polymerization of PPy Composites 64 4.2.4. Morphology Observation 65 4.2.5. Thermosensitivity of poly(NIPAAm-co-AA) Microgels 65 4.2.6. Electrical Conductivity Measurement 66 4.3. Results and Discussion 67 4.3.1. Preparation and Morphology of (NIPAAm-co-AA) Microgels 67 4.3.2. Thermosensitivity of poly(NIPAAm-co-AA) Microgels 67 4.3.3. Preparation of Composites 68 4.3.4. Morphology Observation 69 4.3.5. Electrically Conducting Behavior 70 4.3.5.1. Polypyrrole (PPy) 70 4.3.5.1.1. Effect of Humidity 70 4.3.5.1.2. Effect of Temperature 70 4.3.5.2. Composite Microgels 71 4.3.5.2.1. Effect of Humidity and Composition 71 4.3.5.2.1. Effect of Temperature and Composition 74 4.4. Conclusion 76 4.5. Reference 77 Chapter 5 Preparation and Properties of Poly(acrylic acid) Oligomer Stabilized Superparamagnetic Ferrofluid 80 Abstract 80 5.1. Introduction 81 5.2. Experiment 84 5.2.1. Material 84 5.2.2. Synthesis of Ferrofluid 84 5.2.3. Observation of Fe3O4 Nanoparticles 84 5.2.4. Measurement of FTIR 85 5.2.5. Measurement of Particle Size and Zeta Potential of Fe3O4 Nanoparticle 85 5.2.6. Stability of Ferrofluid 85 5.2.7. TGA and XRD Analysis 86 5.2.8. Measurement of Magnetization of Fe3O4 Particles 86 5.3. Results and Discussion 88 5.3.1. Synthesis of Ferrofluid 88 5.3.2. FTIR Analysis 89 5.3.3. Zeta Potential and Light Scattering Analysis 90 5.3.4. Stability of Ferrofluid 92 5.3.5. XRD Analysis 94 5.3.6. TGA Analysis 95 5.3.7. Squid Analysis 96 5.4. Conclusion 98 5.5. Reference 99 Chapter 6 Thermal-Responsive Complex Polymer Networks Containing Fe3O4 Nanoparticles – Composition / Morphology / Property Relationship 102 Abstract 102 6.1. Introduction 103 6.2. Experiment 105 6.2.1. Material 105 6.2.2. Synthesis of Ferrofluid 105 6.2.3. Synthesis of Magnetic Polymeric Networks 105 6.2.4. Conversion 106 6.2.5. Analysis of Thermoproperties (TGA & DSC) 106 6.2.6. Measurement of Swelling Ratio 107 6.2.7. Morphology of Composite Networks 107 6.2.8. Measurement of Magnetization of Composite Networks 107 6.3. Results and Discussion 109 6.3.1. Synthesis and Stability of Ferrofluid 109 6.3.2. Synthesis of Magnetic Polymeric Networks 110 6.3.3. Conversion of the polymerization 111 6.3.3.1. Effect of Monomer Concentration 111 6.3.3.2. Effect of Crosslink 111 6.3.3.3. Effect of Monomer Composition 111 6.3.3.4. Effect of Magnetite 112 6.3.4. Analysis of Thermoproperties 113 6.3.4.1. TGA Analysis 113 6.3.4.2. DSC Analysis 113 6.3.5. Thermoresponsive Properties 114 6.3.5.1. Effect of Monomer Composition 114 6.3.5.1.1. Effect of Ammonium Solution 114 6.3.5.1.2. Effect of Ferrofluid 115 6.3.5.2. Effect of Crosslink 115 6.3.5.2.1. Effect of Ammonium Solution 115 6.3.5.2.2. Effect of Ferrofluid 116 6.3.6. Morphology of Composite Networks 116 6.3.6.1. Effect of Monomer Composition 117 6.3.6.2. Effect of Crosslink 117 6.3.6.3. Effects of Ammonium Solution and Ferrofluid 117 6.3.7. Magnetization of Composite Networks 117 6.4. Conclusion 120 6.5. Reference 121 Chapter 7 Superparamagnetic Thermoresponsive Composite Latex via W/O Miniemulsion Polymerization 124 Abstract 124 7.1. Introduction 125 7.2. Experiment 128 7.2.1. Material 128 7.2.2. Synthesis and Stability of Ferrofluid 128 7.2.3. Synthesis of Magnetic Polymeric Particles 129 7.2.4. Conversion 130 7.2.5. Morphology of Composite Particles 130 7.2.6. Analysis of Thermoproperties (TGA & DSC) 130 7.2.7. Measurement of Particle Size and Zeta Potential 131 7.2.8. Thermoresponsive Properties 131 7.2.9. Measurement of Magnetization of Composite Latex 131 7.3. Results and Discussion 133 7.3.1. Synthesis and Stability of Ferrofluid 133 7.3.2. Synthesis of Magnetic Polymeric Particles 134 7.3.3. Conversion of the polymerization 137 7.3.4. Thermoproperties 138 7.3.5. Measurement of Zeta Potential 139 7.3.6. Thermoresponsive Property 140 7.3.7. Magnetization of Composite Latex 141 7.4. Conclusion 144 7.5. Reference 145 Chapter 8 Preparation and Targeting Drug Release Application of Thermally Responsive Core-Shell Copolymer Latex with Different Core Compositions 147 Abstract 147 8.1. Introduction 148 8.2. Experiment 151 8.2.1. Material 151 8.2.2. Soapless Dispersion Copolymerization 151 8.2.3. Conversion 152 8.2.4. Morphology of Copolymer Particles 152 8.2.5. Analysis of Thermoproperties (TGA & DSC) 153 8.2.6. Measurement of Swelling Ratio 153 8.2.7. Zeta Potential and Light Scattering Measurements 154 8.2.8. Specific Surface Area and Surface Functional Group Analysis 154 8.2.9. Caffeine Releasing Experiment 154 8.2.10. Protein Conjugation 155 8.3. Results and Discussion 156 8.3.1. Preparation of Copolymer Latex Particles 156 8.3.1.1. First Stage of Copolymerization 156 8.3.1.1.1. Effect of chitosan/ NIPAAm Weight Ratio 156 8.3.1.1.2. Effect of Crosslinking Agent 157 8.3.1.2. Second Stage of Copolymerization 157 8.3.1.2.1. Effect of chitosan/ NIPAAm Weight Ratio 158 8.3.1.2.2. Effect of Crosslinking Agent 158 8.3.2. Observation of Latex Particles 158 8.3.3. TGA and DSC Analysis 159 8.3.4. Swelling Behavior 160 8.3.4.1. Effect of chitosan/NIPAAm (or chitosan/MAA) Weight Ratio 160 8.3.4.2. Effect of Crosslinking Agent 161 8.3.5. Zeta Potential and Size of Swollen Particles 162 8.3.5.1. Effect of chitosan/ NIPAAm Weight Ratio 162 8.3.5.2. Effect of Crosslinking Agent 163 8.3.6. Specific Surface Area and Surface Functional Group of Particles 164 8.3.6.1. Effect of chitosan/NIPAAm Weight Ratio 164 8.3.6.2. Effect of Crosslinking Agent 165 8.3.7. Drug Releasing Estimation 165 8.3.8. Protein Conjugation 167 8.4. Conclusion 169 8.5. Reference 170 Chapter 9 Synthesis and Properties of Thermo-Responsive Core-Shell Copolymer Latex with Different Shell Compositions for Targeting Drug Carrier Application 172 Abstract 172 9.1. Introduction 173 9.2. Experiment 176 9.2.1. Material 176 9.2.2. Soapless Dispersion Copolymerization 176 9.2.3. The Measurements of Properties 176 9.3. Results and Discussion 178 9.3.1. Conversion of Copolymerization 178 9.3.1.1. Effect of MAA/MMA Weight Ratio 179 9.3.1.2. Effect of the Concentration of Shell Monomers (MAA and MMA) 179 9.3.2. Observation of Latex Particles 179 9.3.3. Swelling Measurements 180 9.3.3.1. Effect of MAA/MMA Weight Ratio 180 9.3.3.2. Effect of Concentration of Shell Monomers 181 9.3.4. Zeta Potential and Average Size of Swollen Particles 182 9.3.5. Specific Surface Area and Surface Functional Group of Particles 183 9.3.6. Drug Releasing Estimation 184 9.3.7. Protein Conjugation 186 9.4. Conclusion 188 9.5. Reference 189 Chapter 10 Conclusion and Future Work 191en-US氮-異丙基丙烯醯胺溫度感應性微膠體導電度核殼型態磁性流體超順磁性複合乳膠顆粒藥物釋放無乳化劑乳化聚合水/油 迷你乳化聚合N-isopropylacrylamidethermoresponsive propertymicrogelelectrical conductivitycore-shell morphologyferrofluidsuperparamagneticcomposite latexdrug releasesurfactant-free emulsion polymerizationW/O miniemulsion polymerizationthesis