【作者】 周建华；

【导师】 王立；

【作者基本信息】 浙江大学 ， 高分子化学与物理， 2011， 博士

【摘要】 两亲性星形嵌段共聚物和两亲性星形杂臂聚合物具有两亲性线形嵌段共聚物和支化聚合物的性质,在水溶液中,可以自组装成核-壳结构的胶束。与线形聚合物胶束相比,星形聚合物胶束具有高稳定性和高包载能力,在生物医用材料方面有重要的应用价值,引起了国内外学者的普遍关注。本论文合成了五个系列以聚已内酯为疏水性嵌段的两亲性星形聚合物,并表征其结构和研究其性能。具体研究结果简述如下。采用开环聚合(ROP)和可逆加成-断裂链转移(RAFT)聚合合成了星形聚已内酯-b-聚甲基丙烯酸-2-二甲基氨基乙酯(HPs-Star-PCL-b-PDMAEMA),用1H-NMR和GPC对其结构进行了表征。采用DLS研究了HPs-Star-PCL-b-PDMAEMA的胶束化行为,随水溶液pH值增加和温度升高,胶束的流体力学直径(Dh)减小星形聚合物对疏水性药物阿士匹林的缓释性能研究表明,随水溶液的pH值减小和温度降低,阿司匹林从星形聚合物中的释放速率增加。采用ROP和原子转移自由基聚合(ATRP)合成了星形聚已内酯-b-聚(异丙基丙烯酰胺-co-甲基丙烯酸-2-二甲基氨基乙酯)(HPs-Star-PCL-b-P(NIPAAm-co-DMAEMA)),用1H-NMR和GPC对其结构进行了表征。采用DSC、XRD和偏光显微镜研究了HPs-Star-PCL-b-P(NIPAAm-co-DMAEMA)的结晶性能,发现聚合物的支化结构,以及PNIPAAm链段和PDMAEMA链段的引入降低了PCL的结晶能力。DLS、荧光光谱和AFM的研究结果表明,在水溶液中,该星形聚合物形成了单分子胶束和多分子胶束。在pH=3缓冲溶液中,当NIPAAm与DMAEMA的投料摩尔比大于8/1时,随着NIPAAm与DMAEMA的投料摩尔比的减小,星形聚合物的低临界溶解温度(LCST)从34℃增加到54℃；当NIPAAm与DMAEMA的投料摩尔比小于等于8/1时,星形聚合物没有表现出LCST.在pH=9缓冲溶液中,随着NIPAAm与DMAEMA的投料摩尔比的减小,LCST由35℃逐渐增加到40℃。随水溶液的pH值增加和温度升高,吲哚美辛从星形聚合物胶束中的释放速率增加。聚酰胺-胺型(PAMAM)树形分子与丙烯酸-2-(α-溴异丁酰氧基)乙酯和丙烯酸羟乙酯发生Michael加成反应,制备了多功能引发剂(OH)4-PAMAM-(Br)4。采用ROP和ATRP合成两亲性星形杂臂聚合物(PCL)4-PAMAM-(PDMAEMA)4,用’H-NMR和GPC对其结构进行了表征。该聚合物在水溶液中形成了粒径分布均一的球形胶束,溶液温度升高引起胶束的Dn明显减小。以该胶束为模版,PDMAEMA为还原剂,原位制备了直径约为7nm的银纳米粒子,其表面等离子吸收具有温度依存性。提出了银纳米粒子的可能形成机理。采用ROP和ATRP合成了星形聚已内酯-b-聚甲基丙烯酸特丁酯(HPs-Star-PCL-b-PMBA),水解后,得到星形聚已内酯-b-聚甲基丙烯酸(HPs-Star-PCL-b-PMAA),用1H-NMR和GPC对聚合物结构进行了表征。制备了一系列星形聚已内酯-b-聚甲基丙烯酸／聚乙烯吡咯烷酮(HPs-Star-PCL-b-PMAA/PVP)复合物。当PVP与HPs-Star-PCL-b-PMAA的质量比为3比7时,混合体系为带蓝色乳光的溶液；PVP用量增加到一定值时,如PVP与HPs-Star-PCL-b-PMAA的质量比为5比5和7比3,混合体系中出现了大尺寸的聚集体,甚至沉淀。DLS的研究结果表明,复合物粒子的尺寸随PVP用量的增加而增大。FT-IR和DSC的研究结果表明,HPs-Star-PCL-b-PMAA的PMAA链段和PVP分子间存在极强的氢键相互作用。TEM的结果表明,当PVP与HPs-Star-PCL-b-PMAA的质量比较小时,如3比7,复合物可自组装成球形胶束和囊泡,当PVP与HPs-Star-PCL-b-PMAA的质量比较大时,如5比5和7比3,复合物形成巨型聚集体。提出了复合物的可能自组装机理模型。制备了一系列星形聚已内酯-b-聚甲基丙烯酸／聚丙烯胺盐酸盐(HPs-Star-PCL-b-PMAA/PAH)复合物。UV-Vis、DLS、TEM和ξ-电位的研究结果表明,当PAH与HPs-Star-PCL-b-PMAA的质量比小于等于2比8时,复合物粒子的粒径随着PAH用量增加而减小,复合物粒子具有核-壳-冠层状结构,核层为超支化聚酯和PCL,壳层为PMAA链段和PAH形成的复合物,冠层为没有复合的PMAA链段。当PAH与HPs-Star-PCL-b-PMAA的质量比为3比7时,出现了有几个复合物粒子组成的聚集体。随PAH用量进一步增加,复合物体系中出现了大量沉淀。提出了复合物的可能形成机理模型。采用ROP和ATRP合成了星形聚已内酯-b-聚甲基丙烯酸-2-二甲基乙基溴化铵乙酯(HPs-Star-PCL-b-QPDMAEMA),用1H-NMR和GPC表征了聚合物的结构。采用静电LbL技术,制备了HPs-Star-PCL-b-QPDMAEMA/HPs-Star-PCL-b-PMAA和HPs-Star-PCL-b-QPDMAEMA/PSS多层膜,用UV-Vis、石英晶体微天平(QCM)和AFM表征了多层膜的形成、结构和性能。改变HPs-Star-PCL-b-PMAA溶液的pH值,可以调控HPs-Star-PCL-b-QPDMAEMA/HPs-Star-PCL-b-PMAA多层膜的厚度和表面形貌,多层膜的厚度随组装层数增加呈线性增加趋势；随着HPs-Star-PCL-b-PMAA溶液的pH值的减小,多层膜的厚度和表面粗糙度增加；当HPs-Star-PCL-b-PMAA溶液pH=5时,随着组装层数的增加,多层膜的表面粗糙度和膜表面的粒子尺寸明显增加；当HPs-Star-PCL-b-PMAA溶液pH=9时,在多层膜的生长过程中,膜表面的粗糙度和颗粒尺寸大小差别不大,颗粒粒径均在50-100nm；用pH=2和pH=11水溶液处理多层膜后,膜的厚度、表面形貌和粗糙度发生了明显变化,膜的耐酸稳定性远远好于耐碱稳定性。研究了组装时间、聚电解质溶液的浓度和离子强度对HPs-Star-PCL-b-QPDMAEMA和PSS体系的层层自组装行为的影响,结果表明,多层膜的组装量和厚度随组装层数的增加逐渐增加,且基本呈线性关系；吸附沉积过程在大约15min后达到了平衡；当聚电解质浓度小于0.5mg/mL时,随聚电解质浓度增大,聚电解质的组装量增大,之后,聚电解质浓度对组装量没有明显影响；聚电解质的组装量和膜的粗糙度随氯化钠浓度的增大而增加。当聚电解质溶液的离子强度(C(NaCl)=0.5mol/L)较高时,多层膜中出现了大量的孔径为14-20nm和孔深为6-10nm的小孔。提出了多层膜在不同离子强度溶液中的形成机理模型。更多还原

【Abstract】 Amphiphilic star block copolymers and amphiphilic star heteroarm polymers possessing the properties of both amphiphilic linear block copolymers and branched polymers are able to self-assemble into polymeric micelles in water. Compared to the conventional micelles from amphiphilic linear block copolymers, the micelles formed from amphiphilic star polymers have higher stability and higher loading capacity, which makes them very attractive in diverse fields of medicine and biology. In this thesis, we synthesized and characterized five series of amphiphilic star polymers with polycaprolactones as hydrophobic segments, and investigated their properties. The main results obtained in this thesis are as follows.The star-shaped poly(ε-caprolactone)-b-poly(2-(dimethylamino) ethyl methacryl-ate) (HPs-Star-PCL-b-PDMAEMA) was synthesized by ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The resultant polymer was characterized by 1H-NMR and GPC. Furthermore, the micellar properties of HPs-Star-PCL-b-PDMAEMA in water were studied at various temperatures and pH values by means of dynamic light scattering (DLS). The results indicated that the hydrodynamic diameters of micelles decreased with increasing pH and temperature of aqueous solutions. The release behaviors of model drug aspirin from the star polymer indicated that the rate of drug release increased with the decrease of pH value and temperature of aqueous solutions.The amphiphilic star block copolymers HPs-Star-PCL-b-P(NIPAAm-co-DMAEMA) with a hyperbranched polyester (HPs) core, a hydrophobic poly(ε-caprolactone) (PCL) inner shell and a hydrophilic copolymer of NIPAAm and DMAEMA (P(NIPAAm-co-DMAEMA)) outer shell were synthesized by ROP and atom transfer radical polymerization (ATRP). The star block copolymers were characterized using’H-NMR spectrum and GPC analysis. The crystallization behavior of star block copolymer was investigated by DSC, XRD, and polarized optical microscope (POM). The results indicated that the branched structure and the presence of PNIPAAm and PDMAEMA segments reduced the capacity of the PCL segments to crystallize. The micellar properties of the star block copolymer were studied by DLS, fluorescence spectroscopy and AFM. The results showed that unimolecular micelles and aggregated multimolecular micelles coexisted in the star block copolymer aqueous solution. The lower critical solution temperature (LCST) depended on both the NIPAAm/DMAEMA feed molar ratio and the pH value of water. In pH 3 buffer solution, when the feed molar ratio of NIPAAm to DMAEMA is more than 8/1, LCST increased from 34℃to 54℃with decreasing NIPAAm/DMAEMA feed molar ratio. However, when the feed molar ratio of NIPAAm to DMAEMA is less than or equal to 8/1, no phase transiton could be observed up to 60℃. In pH 9 buffer solution, the increase of DMAEMA content in the star copolymer led to the gradual increase of LCST from 35℃to 40℃. The release behaviors of model drug indomethacin from the star polymer micelles indicated that the rate of drug release increased with the increase of pH value and temperature.The heterofunctional macroinitiator (OH)4-PAMAM-(Br)4 was synthesized by sequential Michael addition reaction of acryloyloxyethyl 2-bromoisobutyrate and 2-hydroxyethyl acrylate with amine-terminated PAMAM. The heteroarm star polymer (PCL)4-PAMAM-(PDMAEMA)4 was obtained via ROP and ATRP, and was characterized using 1H-NMR and GPC. Heteroarm star polymer could self-assemble into spherical micelles in aqueous solution, which were characterized by TEM and DLS. In addition, the increase of temperature resulted in a noticeable decrease in hydrodynamic diameter. Silver nanoparticles were prepared by in situ synthetic method utilizing PDMAEMA as both reductant and stabilizer. The average size of the silver nanoparticles was about 7 nm. The hybrid micelles had an obvious surface plasmon resonance absorption band, and a red-shifting plasmon peak as environmental temperature increaseed. Finally, a model was proposed to explain the formation of silver nanoparticles.The star block copolymer HPs-Star-PCL-b-PtBMA with a hyperbranched polyester (HPs) core, poly (ε-caprolactone) (PCL) and poly (tert-butyl methacrylate) (PtBMA) segments was synthesized by ROP and ATRP. Subsequently, the PtiBMA segments were converted into poly (methacrylic acid) (PMAA) segments by hydrolysis with trifuoroacetic acid. The star block copolymers were characterized by 1H-NMR and GPC. Interpolymer complexes were prepared from HPs-Star-PCL-b-PMAA and poly (N-vinylpyrrolidone) (PVP) in dimethyl formamide (DMF). At 3/7 of the mass ratio of PVP to HPs-Star-PCL-b-PMAA, the blue-opalescent solution was formed. At 5/5 and 7/3 of the mass ratio of PVP to HPs-Star-PCL-b-PMAA, precipitates were formed immediately on mixing DMF solutions of HPs-Star-PCL-b-PMAA and PVP. The hydrodynamic diameters of complexes increased with increasing PVP dosage.The hydrogen bonding interactions of the complexes were investigated using FT-IR and DSC. It was revealed that there was very strong hydrogen bonding interactions between the carboxyl groups of PMAA segments of HPs-Star-PCL-b-PMAA and the carbonyl groups of PVP. The self-assembly behavior of complexes was examined by TEM and DLS. It was observed that spherical micelles and vesicles were formed at the low mass ratio of PVP to HPs-Star-PCL-b-PMAA. With increasing PVP content in the complexes, the particles of interpolymer complexes coiled up and aggregated to large dimension, even precipitated. Finally, a model was proposed to explain the aggregation process of the HPs-Star-PCL-b-PMAA/PVP complexes. The polyelectrolyte complexes were prepared from HPs-Star-PCL-b-PMAA and poly(allylamine hydrochloride) (PAH), which were characterized by UV-Vis, DLS, TEM andξ-potential. When the mass ratio of PAH to HPs-Star-PCL-b-PMAA was less than or equal to 2/8, water-soluble complexes had core-shell-corona structure, with a core formed by the hyperbranched polyester and PCL, a shell assembled from the coupled oppositely charged polyelectrolyte fragments, and a corona built up from the fragments of PMAA segments not involved in the interpolyelectrolyte. At 3/7 of the mass ratio of PAH to HPs-Star-PCL-b-PMAA, multimicellar aggregates were formed due to the bridging action of PAH among polyelectrolyte complexes particles. When the mass ratio of PAH to HPs-Star-PCL-b-PMAA was more than or equal to 4/6, the precipitate was formed as aggregated solid structure. Finally, a model was proposed to explain the formation of HPs-Star-PCL-b-PMAA/PAH complex. The amphiphilic star block polyelectrolyte HPs-Star-PCL-b-QPDMAEMA with a hyperbranched polyester (HPs) core, a hydrophobic PCL inner shell and a hydrophilic quaternized poly (2-(dimethylamino) ethyl methacrylate) (QPDMAEMA) outer shell was synthesized by ROP and ATRP. The star block copolymers were characterized by 1H-NMR and GPC. HPs-Star-PCL-b-PMAA was assembled alternately with HPs-Star-PCL-b-QPDMAEMA at different pH conditions to form pH-responsive multilayer films characterized using QCM and AFM. The film thickness increased linearly with increasing bilayer numbers for each pH value of the HPs-Star-PCL-b-PMAA solution. The film thickness and roughness increased with decreasing pH value of HPs-Star-PCL-b-PMAA solution. For the multilayer films buildup at the HPs-Star-PCL-b-PMAA dipping solution of pH 5, the surface roughness and grain size of the film increased distinctly as the number of deposited bilayers increased. For the film prepared from the HPs-Star-PCL-b-PMAA solution of pH 9. the diameters of the granules were approximately 50-100nm, and the surface roughness and grain size of the film showed no significant difference during assembly. The multilayer films were treated by immersion into pH 2 and pH 11 solutions after assembly. AFM measurements showed that all the multilayer films were stable in pH 2 aqueous solution. The multilayer films deposited at HPs-Star-PCL-b-PMAA solutions of pH 5 and pH 7 were unstable in pH 11 aqueous solution. The effect of dipping time, polyelectrolyte concentration and ionic strength on the formation of multilayer films by sequential adsorption of HPs-Star-PCL-b-QPDMAEMA and poly (sodium-p-styrenesulfonate) (PSS) was investigated by means of UV-Vis absorption spectroscopy, QCM and AFM. The results demonstrated that the multilayer films grew linearly with increasing layer number. The growth rate first increased as dipping time increased, then saturated beyond the dipping time of approximately 15min. The amount of polyelectrolyte deposited per bilayer rapidly increased with increasing polyelectrolyte concentration up to 0.5 mg/mL, while the solution concentration above 0.5 mg/mL had no appreciable effect on the adsorbed amount. With increasing ionic strength, the polyelectrolyte chains underwent a transition from an extended to a coiled conformation, which led to an increase in the thickness and surface roughness of multilayer film. For the film prepared from a salt concentration of 0.5 mol/L NaCl, small pores with typical diameters of 14-20 nm and apparent depths of 6-10 nm were observed. Finally, a model was proposed to explain the LbL assembly of HPs-Star-PCL-b-QPDMAEMA and PSS in aqueous solutions with various salt concentrations.更多还原