聚(氮-異丙基丙烯醯胺)衍生溫度感應型共聚微膠體：製備，性質及應用

Poly(N-isopropylacrylamide) Related Thermoresponsive Copolymer Microgels: Preparation, Properties, and Application

林佳龍(Chia-Lung Lin)

指導教授 ： 邱文英

國立臺灣大學/工學院/材料科學與工程學研究所/博士(2005年)

https://doi.org/10.6342/NTU.2005.01383

摘要

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。

關鍵字

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

並列摘要

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.

並列關鍵字

N-isopropylacrylamide ； thermoresponsive property ； microgel ； electrical conductivity ； core-shell morphology ； ferrofluid ； superparamagnetic ； composite latex ； drug release ； surfactant-free emulsion polymerization ； W/O miniemulsion polymerization

參考文獻

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