基于PEG类聚物的双温敏性嵌段聚合物的合成及性质研究

发布时间：2018-10-10 06:06

【摘要】：刺激响应性聚合物在生物医药、组织工程、人造肌肉以及药物载体等领域有广阔的发展前景,其中,研究最多的是温度敏感性聚合物。基于单一刺激响应性聚合物已经不能满足人们现代生活的需求,双温敏性聚合物的研究逐渐增多,为蛋白质的定向固定化、温敏性聚合物的设计合成等提供了更灵活的空间。寡聚乙二醇甲醚甲基丙烯酸酯(OEGMA)和2-甲基-2-丙烯酸-2-(2-甲氧基乙氧基)乙酯(MEO2MA)作为新型的温敏性单体家族,都具有低聚(乙二醇)侧链,文献报道的聚2-甲基-2-丙烯酸-2-(2-甲氧基乙氧基)乙酯(PMEO2MA)具有的低临界溶解温度(LCST)为26℃,聚寡聚乙二醇甲醚甲基丙烯酸酯(POEGMA)的LCST为90℃,因而它们无规共聚物P(MEO2MA-co-OEGMA)的LCST可以通过改变两种单体的摩尔比对其进行调节。基于这两种单体的均聚物以及它们的无规共聚物都是PEG的类似物,因此具有良好的水溶性和生物相容性。聚乙二醇(PEG)是一种亲水性高分子,生物相容性良好,具有无毒、无免疫等特点,因此被广泛应用于生物医学等领域。带有功能性羟基的N-羟甲基丙烯酰胺(HMAM)是亲水性单体,将其引入温敏性聚合物中可以增强聚合物的亲水性,进而调节其LCST。本文选用具有生物相容性的亲水性PEG、温敏性单体MEO2MA和 OEGMA以及亲水性单体HMAM来合成两种双温敏性的嵌段聚合物。首先,通过可逆加成-断裂链转移自由基聚合(RAFT)合成ABC型的双温敏性三嵌段聚合物PEG-b-PMEO2MA-b-P(MEO2MA-co-OEGMA),着重研究了该聚合物的水溶液性质、胶束化以及凝胶化行为；其次,使用原子转移自由基聚合(ATRP)技术合成ABCBA型的双温敏性嵌段聚合物P(MEO2MA-co-HMAM)-b-PMEO2MA-b-PEG-b-PMEO2MA-b-P(MEO2MA-co-HMAM),着重研究了该聚合物的水溶液性质及胶束化行为。具体工作如下：1.利用RAFT聚合方法合成了ABC型的双温敏性三嵌段聚合物PEG-b-PMEO2MA-b-P(MEO2MA-co-OEGMA)。该聚合物的结构和分子量通过核磁共振氢谱测试(1H NMR)、红外光谱测试(FT-IR)和凝胶渗透色谱测试(GPC)进行表征；通过聚合物水溶液的透光率随温度的变化曲线,发现聚合物的双温敏性与两个温敏性嵌段的聚合度以及P(MEO2MA-co-OEGMA)链段中两种单体的投料比有关,通过改变聚合度以及两种单体的投料比来控制聚合物的双温敏性,使其两个温敏性嵌段发生连续的脱水聚集；通过动态光散射(DLS)研究了聚合物水溶液中聚集体粒径随温度的变化趋势,表明了聚合物水溶液在热诱导作用下出现两个阶段的稳定自组装过程；利用透射电子显微镜(TEM)、荧光探针技术和表面张力仪研究了聚合物水溶液的胶束形貌以及胶束化行为；最后,通过小瓶翻转实验和流变学测试研究了聚合物水溶液在温度和浓度诱导下的溶胶-凝胶转变行为,结果表明：溶胶-凝胶转变行为与聚合物水溶液的浓度有重要关系,随着聚合物水溶液浓度增加,溶胶-凝胶转变温度降低；反之,溶胶-凝胶转变温度升高。2.通过ATRP技术,以Br-PEG-Br为大分子引发剂,CuCl/bpy作为催化系统合成了ABCBA型的双温敏性五嵌段聚合物P(MEO2MA-co-HMAM)-b-PMEO2MA-b-PEG-b-PMEO2MA-b-P(MEO2MA-co-HMAM)。通过1H NMR、FT-IR和GPC对聚合物的组成结构、分子量以及分子量分布情况进行了表征；利用透光率测试、DLS研究了聚合物水溶液的温敏性行为；通过TEM测试证实了聚合物水溶液在热诱导下形成的“核-壳”球形胶束结构；通过荧光探针技术测得聚合物水溶液分别在两个LCSTs时,基于疏水微区大小的差异使得CMC值不同；最后,研究了聚合物水溶液在热诱导下的粒径变化,说明聚合物水溶液的相转变具有可逆性。
[Abstract]:The stimulation responsive polymer has a wide developing prospect in the fields of biological medicine, tissue engineering, artificial muscle and drug carrier, among which, most of the research is temperature-sensitive polymer. Based on the fact that the single stimulus-responsive polymer has not been able to meet the needs of modern life, the research of double-temperature sensitive polymer is increasing gradually, providing more flexible space for directional immobilization of protein, design synthesis of temperature-sensitive polymer and so on. Oligopolyethylene glycol methyl ether methacrylate (OEGMA) and 2-methyl-2-acrylic-2-(2-methoxyethoxy) ethyl ester (MEO2MA) as a novel temperature sensitive monomer family have a low poly (ethylene glycol) side chain, Poly2-methyl-2-acrylic-2-(2-methoxyethoxy) ethyl ester (PMEO2MA) reported in the literature has a low critical dissolution temperature (LCST) of 26 & deg; C, and the LCST of polyoligoethylene glycol methyl ether methacrylate (POEGMA) is 90 & deg; C, Thus, the LCST of their random copolymer P (MEO2MA-co-OEGMA) can be adjusted by varying the molar ratio of the two monomers. Both the homopolymers based on these two monomers and their random copolymers are PEG analogs, thus having good water solubility and biocompatibility. Polyethylene glycol (PEG) is a kind of hydrophilic polymer, good biocompatibility, non-toxic, immunity-free and so on, so it is widely used in biomedicine and other fields. N-hydroxymethylglucamine (HMAM) with functional hydroxyl groups is a hydrophilic monomer which is introduced into the temperature-sensitive polymer to enhance the hydrophilicity of the polymer, thereby adjusting the LCST of the polymer. Two kinds of double-temperature sensitive block polymers were synthesized by using hydrophilic PEG, temperature sensitive monomer MEO2MA and OEGMA as well as hydrophilic monomer HMAM. First, by reversible addition-fragmentation chain transfer radical polymerization (RAFT) synthesis of ABC-type bis-temperature sensitive triblock polymer PEG-b-PMEO2MA-b-P (MEO2MA-co-OEGMA), the aqueous solution properties, micelle and gelation behavior of the polymer were studied. Two-temperature sensitive block polymers P (MEO2MA-co-HMAM)-b-PMEO2MA-b-PEG-b-PMEO2MA-b-P (MEO2MA-co-HMAM) of ABCB Atype were synthesized using atom transfer radical polymerization (ATRP) technique. The specific work is as follows: 1. The ABC-type bis-temperature sensitive triblock copolymer PEG-b-PMEO2MA-b-P (MEO2MA-co-OEGMA) was synthesized by the RAFT polymerization method. The structure and molecular weight of the polymer were characterized by nuclear magnetic resonance hydrogen spectroscopy (1H NMR), infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC); It was found that the double temperature sensitivity of the polymer was related to the polymerization degree of two temperature sensitive blocks and the feeding ratio of the two monomers in the P (MEO2MA-co-OEGMA) chain segment, and the double temperature sensitivity of the polymer was controlled by changing the degree of polymerization and the feeding ratio of the two monomers, so that the two temperature sensitive blocks had continuous dehydration and aggregation. By means of dynamic light scattering (DLS), the variation trend of particle size with temperature in aqueous polymer solution was studied. The stable self-assembly process of polymer aqueous solution in two stages under the action of heat induction was studied, and the transmission electron microscope (TEM) was used. Micellar morphology and micellar behavior of polymer aqueous solution were studied by fluorescence probe technique and surface tension instrument. Finally, the sol-gel transition behavior of polymer aqueous solution under temperature and concentration was studied by the experiment of vial inversion and rheological test. The results showed that: The sol-gel transition temperature has an important relationship with the concentration of aqueous polymer solution. With the increase of the concentration of aqueous polymer solution, the transition temperature of sol-gel decreases, and vice versa, the transition temperature of sol-gel increases. Two-temperature sensitive pentblock polymers P (MEO2MA-co-HMAM)-b-PMEO2MA-b-PEG-b-PMEO2MA-b-P (MEO2MA-co-HMAM) were synthesized by ATRP technology with Br-PEG-Br as macroinitiator and CuCl/ bpy as catalytic system. The composition structure, molecular weight and molecular weight distribution of polymer were characterized by 1H NMR, FT-IR and GPC. The temperature-sensitive behavior of polymer aqueous solution was studied by DLS using light transmittance test. "Nuclear-Shell" The results show that the change of the particle size of the aqueous polymer solution under the heat induction indicates that the phase transition of the aqueous polymer solution is reversible.
【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O631.3

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