可注射型PNIPAM水凝胶的制备及性能研究

发布时间：2018-11-08 06:38

【摘要】：环境敏感型水凝胶亲水性强、柔性好、对外界刺激具有响应特性,使其在传感器、药物控释开关等领域具有广阔的应用前景。但是由于制备水凝胶时所使用的小分子交联剂往往具有一定的毒性,且交联的高分子网络很难降解,因此开发无毒且可生物降解的环境敏感型“智能”水凝胶具有重要意义。本研究通过分子设计,用含醛基的可生物降解的氧化淀粉为大分子交联剂,通过“醛肼交联”技术,在室温下使聚(N-异丙基丙烯酰胺)温敏共聚物上的肼基与氧化淀粉交联剂上的醛基发生交联反应,制备了可注射且可生物降解的温度敏感型聚(N-异丙基丙烯酰胺)(PNIPAM)水凝胶。论文主要工作如下：(1)制备了含肼基的聚(N-异丙基丙烯酰胺)温敏共聚物。首先以N-异丙基丙烯酰胺(NIPAM)为主单体,以丙烯酸(AA)为功能共聚单体,在乙醇中通过自由基溶液共聚合,制备了三种羧基含量的聚(N-异丙基丙烯酰胺)共聚物：poly(NIPAM-co-AA);然后在缩合剂的作用下,通过己二酰肼的一端肼基与poly(NIPAM-co-AA)共聚物侧链羧基发生脱水缩合反应,成功制得了侧链带肼基的改性poly(NIPAM-co-AA)共聚物：poly(NIPAM-co-AA)-hdz。用电导滴定法对聚合物的羧基含量进行了测定,以此计算羧基转变为肼基的转化率；此外还用红外光谱对聚合物的结构进行了表征。(2)制备了含醛基的氧化淀粉。以可生物降解的低分子量玉米淀粉为原料,在氧化剂偏高碘酸钠的作用下,制备了三种醛基含量的氧化淀粉(双醛淀粉),并在盐酸羟胺辅助下用电导滴定法对醛基含量进行了测定,用红外光谱对聚合物的结构进行了表征。(3)以无毒且可生物降解的双醛淀粉为大分子交联剂,通过“醛肼交联”技术,制备了可注射且可生物降解的温度敏感型PNIPAM水凝胶,并对不同交联密度的水凝胶的溶胀性能、降解性能及药物控释性能进行了研究,用红外光谱对聚合物的结构进行了表征。结果表明,水凝胶具有较强的溶胀能力、较好的药物负载能力及药物缓释效果,且能对温度刺激作出响应。水凝胶能被酸催化水解,既包括淀粉的降解,也包括醛肼交联键的水解,而且交联密度越大,降解越慢。
[Abstract]:Environmental sensitive hydrogel has strong hydrophilicity, good flexibility and response to external stimuli, which makes it have a broad application prospect in sensor, drug controlled release switch and other fields. However, because the small molecular crosslinkers used in the preparation of hydrogels are often toxic and the crosslinked polymer networks are difficult to degrade, it is of great significance to develop non-toxic and biodegradable environment-sensitive "intelligent" hydrogels. In this study, aldehyde-hydrazine crosslinking was used as macromolecular crosslinking agent using aldehyde-containing biodegradable oxidized starch as crosslinking agent by molecular design. At room temperature, the hydrazine group on the thermo-sensitive copolymer of poly (N-isopropylacrylamide) was crosslinked with the aldehyde group on the cross-linking agent of oxidized starch. An injectable and biodegradable temperature sensitive poly (N isopropyl acrylamide) (PNIPAM) hydrogel was prepared. The main work of this paper is as follows: (1) the thermo-sensitive copolymer containing hydrazine group was prepared. Firstly, N-isopropylacrylamide (NIPAM) was used as the main monomer and acrylic acid (AA) as the functional copolymerization monomer. The copolymerization was carried out in ethanol by free radical solution copolymerization. Three kinds of carboxyl content poly (N-isopropylacrylamide) copolymer: poly (NIPAM-co-AA were prepared. Then, under the action of condensation agent, the side chain carboxyl group of poly (NIPAM-co-AA) copolymers was dehydrated and condensed by one end hydrazine group of adipic hydrazide. The modified poly (NIPAM-co-AA) copolymers with hydrazine group on the side chain: poly (NIPAM-co-AA)-hdz. have been successfully prepared. The carboxyl content of the polymer was determined by conductance titration to calculate the conversion of carboxyl group to hydrazine group, and the structure of the polymer was characterized by infrared spectroscopy. (2) oxidized starch containing aldehyde group was prepared. Three kinds of oxidized starch (dialdehyde starch) were prepared from biodegradable low molecular weight corn starch under the action of oxidizer sodium metperiodate. The content of aldehyde group was determined by conductance titration assisted by hydroxylamine hydrochloride, and the structure of polymer was characterized by infrared spectroscopy. (3) Non-toxic and biodegradable dialdehyde starch was used as macromolecular crosslinking agent. The injectable and biodegradable PNIPAM hydrogels were prepared by "aldehyde hydrazine crosslinking" technique. The swelling, degradation and drug release properties of the hydrogels with different crosslinking densities were studied. The structure of the polymer was characterized by IR spectra. The results showed that hydrogel had strong swelling ability, good drug loading capacity and drug release effect, and could respond to temperature stimulation. Hydrogels can be hydrolyzed by acid, including the degradation of starch and the hydrolysis of aldehyde-hydrazine crosslinking bonds, and the higher the crosslinking density, the slower the degradation.
【学位授予单位】：北京化工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R318.08

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