PCL-b-PHEAA两亲性嵌段共聚物胶束的制备及性能研究

发布时间：2018-02-28 04:33

本文关键词： 聚己内酯羟乙基丙烯酰胺原子转移自由基聚合自组装胶束　出处：《郑州大学》2017年硕士论文　论文类型：学位论文

【摘要】：两亲性嵌段共聚物结构具有特殊性和多样性,可在选择性溶剂中自组装成为不同形貌的纳米粒子,在生物医药、催化等领域有潜在的应用价值。近年来,具有生物降解性、生物相容性、环境响应性的胶束一直是新型功能性高分子研究的热点。相比小分子,共聚物自组装后的胶束更加稳定,稳定的载药胶束能延长药物在机体内的循环时间,有利于药物的输送和释放,因此合成特定结构的两亲性嵌段共聚物有利于获得结构稳定、粒径合适的胶束聚集体。本文通过原子转移自由基聚合法(ATRP)合成了一种新颖的两亲性嵌段共聚物,研究了共聚物在水溶液中的胶束化行为,并考察了其载药和释药性能。主要研究结果如下:通过原子转移自由基聚合法合成了PCL-b-PHEAA两亲性嵌段共聚物。首先将聚己内酯(PCL)和2-溴异丁酰溴(BIBB)反应,在其链端引入溴原子得到引发剂PCL-Br;然后利用PCL-Br引发羟乙基丙烯酰胺(HEAA)聚合,得到两亲性嵌段共聚物PCL-b-PHEAA。采用核磁共振(1H-NMR)、红外光谱(IR)、凝胶渗透色谱仪(GPC)表征了引发剂和共聚物的化学结构、分子量,差示扫描量热仪(DSC)和热重分析仪(TG)表征了共聚物的热性能。引发剂为多孔疏松结构,嵌段共聚物为致密的层状结构。共聚物在50°C附近熔融,相比于PCL,共聚物分为两个失重阶段,热稳定性有所下降。共聚物通过透析法在水溶液中自组装,形成球形胶束。利用荧光光谱法、激光粒度仪分别对其临界胶束浓度(CMC)、粒径大小及其分布进行测定;静滴接触角测量仪研究了亲水性能;扫描电子显微镜(SEM)、透射电子显微镜(TEM)观察胶束的形貌;另外研究了不同pH值对粒径和形貌的影响。结果表明:共聚物通过透析法在水溶液中自组装成稳定的胶束体系,有明显的丁达尔现象。PCL的接触角为56.5°,共聚物溶液的接触角在26~31°,在pH=6.8时共聚物溶液的接触角较小。激光粒度仪测试结果表明,胶束尺寸呈单峰分布,PCL109-b-PHEAA14共聚物胶束在水溶液中的平均粒径为490 nm,分散性良好。pH从4.0增加至9.2,胶束的粒径减小,多分散指数变化不大。0.1 mg/mL溶液浓度制得的胶束在SEM下观察为球形,分散性较好。酸性条件下,胶束在结晶的驱动下有从球形转变成棒状或者片状的趋势。透射电镜测试表明,球形胶束的平均直径为104 nm。嵌段共聚物PCL109-b-PHEAA32的临界胶束浓度为1.62μg/mL,PCL109-b-PHEAA14的临界胶束浓度为12.2μg/mL。载药胶束冷冻干燥后,SEM观察显示为球形,平均粒径为564 nm。载药胶束溶液静置半个月后,稳定性有所降低,粒径明显增加,多分散指数增加。载药胶束的释放行为研究表明,缓冲液中的释放量随着时间的延长逐渐增加,后趋于平缓。这种具有生物相容性、可生物降解性的两亲性嵌段共聚物在生物医药领域有潜在的应用价值。
[Abstract]:Amphiphilic block copolymers have special and diverse structures, which can self-assemble into nanoparticles with different morphologies in selective solvents, and have potential applications in biomedicine, catalysis, etc. In recent years, amphiphilic block copolymers are biodegradable. Biocompatibility and environmental responsiveness of micelles have been a hot topic in the study of novel functional polymers. Compared with small molecules, the micelles after self-assembly of copolymers are more stable, and stable micelles can prolong the circulation time of drugs in the body. Thus, the synthesis of amphiphilic block copolymers with specific structures is conducive to structural stability. A novel amphiphilic block copolymer was synthesized by atom transfer radical polymerization (ATRP). The micellization behavior of the copolymer in aqueous solution was studied. The main results are as follows: the amphiphilic block copolymers of PCL-b-PHEAA were synthesized by atom transfer radical polymerization. The initiator PCL-Brand the hydroxyethyl acrylamide (HEAA) polymerization initiated by PCL-Br was obtained by introducing bromine atoms into the chain end. The amphiphilic block copolymer PCL-b-PHEAA was obtained. The chemical structure and molecular weight of the initiator and copolymer were characterized by 1H-NMR-NMR, IR and GPC. The thermal properties of the copolymers were characterized by differential scanning calorimeter (DSC) and thermogravimetric analyzer (TG). The initiator was porous and the block copolymers were dense layered structures. The copolymers melted at about 50 掳C. compared with PCLs, the copolymers were divided into two weightlessness stages. The copolymers were self-assembled in aqueous solution by dialysis method to form spherical micelles. The critical micelle concentration (CMC), particle size and its distribution were measured by fluorescence spectroscopy and laser particle size analyzer. The hydrophilicity was studied by the contact angle measuring instrument, and the morphology of the micelles was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). In addition, the effects of different pH values on particle size and morphology were studied. The results showed that the copolymers were self-assembled in aqueous solution to form stable micelles by dialysis. The contact angle of the copolymers solution is 2631 掳and the contact angle of the copolymers solution is 2631 掳. The contact angle of the copolymers solution is smaller at pH=6.8. The results of laser particle size analyzer show that the contact angle of the copolymers is 56.5 掳. The average particle size of PCL109-b-PHEAA14 copolymer micelles in aqueous solution was 490nm, the dispersion of the micelles was increased from 4.0 to 9.2, the particle size of the micelles decreased, and the polydispersity index was not changed. The micelles prepared by the concentration of 0.1 mg/mL solution were spherical under SEM. The dispersibility is good. Under acidic condition, the micelle changes from spherical to rod or flake driven by crystallization. Transmission electron microscopy (TEM) test shows that, The average diameter of spherical micelles is 104nm.The critical micelle concentration of block copolymer PCL109-b-PHEAA32 is 1.62 渭 g / mLP109-b-PHEAA14, and the critical micelle concentration of PCL109-b-PHEAA14 is 12.2 渭 g / mL. The release behavior of the drug-loaded micelles increased gradually with the prolonging of time, and then tended to be gentle, which had biocompatibility, the stability decreased, the particle size increased obviously, and the polydispersity index increased, and the release behavior of the drug-loaded micelles increased gradually with the prolongation of time. Biodegradable amphiphilic block copolymers have potential applications in biomedicine.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O631;TQ460.1

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