原位聚合法制备温敏性聚合物核壳胶束的响应温度调控及其负载行为

采用原位聚合法成功地制备出聚乳酸/聚(异丙基丙烯酰胺-co-丙烯酰胺)[P(D,L-LA)/PNIPAM-co-AM)\]温敏性核壳胶束. 用SEM, TEM和AFM等方法表征了粒子的外在形貌和内部结构. DLS研究结果表明, 所得核壳粒子的尺寸具有温度敏感性, 通过改变单体的投料比, 可方便地调整胶束粒子的响应温度. 对胶束粒子的染料负载行为做了初步的研究.     

单分子胶束的制备及应用研究进展

单分子胶束由单个分子构成且有核-壳结构的胶束,这种独特的结构,使其显示出优异的稳定性,在稀释的条件下,不会发生解离。单分子胶束因其在复杂多变的微环境中具有良好的热力学稳定性和尺寸分布均匀性,使得单分子胶束在药物运输、靶向释放、染料去除、荧光标记、无机纳米颗粒模板的制备、能量收集和储存等方面都有重要应用。本文从不同聚合物结构及功能方向,综述了单分子胶束制备及应用的研究进展。     

用于固定抗体的新型温敏性核—壳结构聚合物微球的合成及其初步应用研究

利用无皂乳液聚合和种子聚合的方法合成了一种以聚苯乙烯为核,聚(N-异丙基丙烯酰胺-co-N-丙烯酸琥珀酰亚胺酯)为壳的单分散的核-壳结构的聚合物微球.用扫描电镜和透射电镜观察了球的形貌特征,发现微球具有清晰的核-壳结构和较好的单分散性,红外光谱显示了在1738cm-1处有酯羰基的特征吸收峰.动态光散射测定发现该聚合物微球具有温敏性,当温度高于聚N-异丙基丙烯酰胺的最低临界溶液温度(LCST)时,球的流体力学直径变小.利用微球壳层所含有的琥珀酰亚胺酯基与伯氨基的高反应活性,将抗体Rabbit IgG化学固定在球的壳层上.由于壳层的聚N-异丙基丙烯酰胺具有温敏性,反应温度不同结合的抗体的量也不同,在0℃和36.5℃,微球对抗体的结合率分别为61.6%和38.6%.     

交联度对原位聚合法制备聚合物胶束性质的影响及相应的空心球制备

用原位聚合法成功地制备出不同响应温度的温敏性聚乳酸/聚(异丙基丙烯酰胺-co-丙烯酰胺)[P(D,L-LA)/P(NIPAM-co-AM)]核壳胶束. 实验中发现, 壳层的交联剂含量对粒子的尺寸有很大的影响, 当交联剂的摩尔分数从5%提高到15%时, 粒子在25 ℃时的流体力学直径从170.2 nm增加到886.5 nm. 通过对胶束粒子的核进行生物降解, 方便地得到了相应的空心球. 用FTIR监测核的降解过程, 用SEM和AFM检测核降解完全后粒子的外在形貌和内在结构变化. DLS结果表明, 空心球粒子同样具有良好的温度响应性, 其响应温度可通过改变原位聚合时单体AM的含量加以调节.     

具有可见光响应聚合物纳米粒子的制备及性能研究

利用可见光响应供体-受体Stenhouse加合物(DASAs)设计并制备了2种表面含有可见光响应单元的聚合物纳米粒子,并对纳米粒子的光响应性进行了研究.首先合成了修饰DASA分子的聚合物PGMD,研究结果表明PGMD可溶于与水互溶的有机溶剂(如DMSO)中并具有良好的光响应性,PGMD链段可在可见光刺激下响应为亲水状态.因此,含有PGMD链段的嵌段共聚物PCL-b-PGMD可在水中自组装形成胶束,并能与PCL-b-PEG在水中共组装形成复合壳层胶束,但PGMD链段在水中无法可逆响应为疏水状态.为获得具有可逆响应性的聚合物纳米粒子,利用硅烷偶联剂水解修饰的方法得到表面含有疏水三烯状态DASA分子与亲水PEG短链的复合壳层二氧化硅纳米粒子,实验结果表明复合壳层二氧化硅纳米粒子在水环境中有良好的分散稳定性,并且表面修饰的DASA分子仍具有良好的响应性.本研究为设计表面性质可调的响应性聚合物纳米粒子提供了新的设计思路.     

基于葡萄糖和苯硼酸基元之间的可逆共价键构筑多重响应性高分子复合物胶束

通过可逆加成-断裂链转移(RAFT)的聚合方法,合成了分别含有苯硼酸基元和葡萄糖基元的聚(N-异丙基丙烯酰胺)-b-聚(丙烯酰胺基苯硼酸)(PNIPAM-b-PAPBA)和聚(N-异丙基丙烯酰胺)-b-聚(丙烯酰葡萄糖胺)(PNIPAM-b-PAGA)二嵌段聚合物.由于苯硼酸和葡萄糖基元之间在弱碱性条件下(pH9.3)形成硼酸酯共价键,两种二嵌段聚合物的水溶液混合后能自发形成以PAPBA/PAGA络合物为核,PNIPAM为壳层的高分子复合物胶束.由于硼酸酯共价键在pH值和葡萄糖浓度改变时能可逆形成和断裂,以及胶束PNIPAM壳层的温敏性,所制备的基于苯硼酸/葡萄糖可逆共价键的高分子复合物胶束对pH、葡萄糖和温度具有多重响应性.     

含十二烷端基聚乙二醇-b-聚(N-丙烯酰脯氨酸甲酯)两嵌段在水溶液中的可逆再组装

以RAFT聚合制备了十二烷基末端聚乙二醇-b-聚(N-丙烯酰脯氨酸甲酯)两嵌段聚合物D12-EA,并用体积排除色谱和核磁氢谱表征了聚合物的结构。结合紫外-可见光(UV-Vis)、动态光散射(DLS)、静态光散射(LLS)、透射电镜(TEM)以及变温核磁氢谱(1 H NMR)研究了其在水溶液中的可逆再组装行为。不同于普通刺激响应性两嵌段在水溶液中由单分子链组装为纳米聚集体,在温度低于温敏性聚丙烯酰脯氨酸甲酯嵌段(A嵌段)浊点(CP)时,D12-EA两嵌段水溶液自组装形成粒径为20nm的球形胶束;而当温度高于CP时,球形胶束能够可逆地再组装为粒径约90nm的囊泡。变温1 H NMR揭示了当温度高于CP时,A嵌段由亲水壳层迁移至疏水核层,从而使体系再组装为自由能更低的结构。     

介孔核结构聚合物胶束的制备及其在汞离子检测中的应用

通过可逆加成-断裂链转移聚合(RAFT)和原子转移自由基聚合(ATRP)设计合成了具有p H响应性和还原响应性的双亲性聚合物分子刷,聚聚(乙二醇)单甲醚甲基丙烯酸酯-block-(聚甲基丙烯酸叔丁酯-graft-聚甲基丙烯酸N,N-二甲氨基乙酯)(POEGMA-b-(Pt BMA-g-PDMAEMA)),其中侧链PDMAEMA与主链通过二硫键相连.运用核磁共振氢谱(1H-NMR)和凝胶渗透色谱(GPC)表征了聚合物的结构、分子量及分子量分布.在碱性条件下,聚合物分子刷自组装成以POEGMA为壳,Pt BMA和PDMAEMA为核的多组分胶束.由于Pt BMA和PDMAEMA互不相容,在核中形成微相分离,体积分数较大的Pt BMA形成连续相,体积分数较小的PDMAEMA形成分散相.调节p H至酸性条件后,分散相PDMAEMA由坍陷变为伸展状态,从胶束的核中溶解出来.加入还原剂断开侧链PDMAEMA与主链相连的二硫键,制得孔内壁含有巯基的介孔核结构聚合物胶束.利用透射电镜(TEM)和动态光散射(DLS)表征了胶束的形貌和粒径.通过TEM结果得出介孔核结构聚合物胶束的孔径大小约为2 nm.利用巯基对氯金酸的还原作用和对金纳米粒子的稳定作用,制得孔内修饰金纳米粒子的介孔核结构聚合物胶束.利用巯基和溴的点击反应,制得孔内修饰聚噻吩衍生物的介孔核结构聚合物胶束,其对Hg~(2+)检测表现出较高的灵敏度和特异性.     

刺激响应性聚合物载药纳米胶束研究进展

刺激响应性聚合物纳米胶束是目前药物控制释放体系的研究热点之一,其原理是将疏水性药物以物理或化学方法包覆在具有核/壳结构的纳米微球中,通过环境刺激响应控制药物的包覆与释放,可增加疏水性药物溶解度、提高药物利用率、降低药物毒副作用,具有显著的研究价值和应用前景.本文中我们主要介绍了不同类型刺激响应性聚合物纳米胶束在药物控制释放体系的研究进展.     

碳酸钙在聚合物胶束控制下的仿生合成

合成了温敏性的聚(N-异丙基丙烯酰胺)-b-聚(L-谷氨酸)(PNIPAM-b-PLGA)嵌段共聚物,在较高温度下制备了以PNIPAM为核、以PLGA为壳的自组装胶束,研究了胶束对碳酸钙晶体生长的控制作用.使用扫描电镜和X射线衍射表征了碳酸钙晶体的形貌和晶型.当聚合物胶束浓度较高时,得到纤维状的文石;当胶束浓度较低时,...     

Micelle or polymersome formation by PCL-PEG-PCL copolymers as drug delivery systems

Polymeric micelles and polymersomes may have great potential as the drug delivery vehicles for solubilization of hydrophobic drugs.     

Co-assembly of Patchy Polymeric Micelles and Protein Molecules

The development in the synthesis and self-assembly of patchy nanoparticles has resulted in the creation of complex hierarchical structures. Co-assembly of polymeric nanoparticles and protein molecules combines the advantages of polymeric materials and biomolecules, and will produce new functional materials. Co-assembly of positively charged patchy micelles and negatively charged bovine serum albumin (BSA) molecules is investigated. The patchy micelles, which were synthesized using block copolymer brushes as templates, leads to co-assembly with protein molecules into vesicular structures. The average size of the assembled structures can be controlled by the molar ratio of BSA to patchy micelles. The assembled structures are dissociated in the presence of trypsin. The protein–polymer hybrid vesicles could find potential applications in medicine.     

Co‐assembly of Patchy Polymeric Micelles and Protein Molecules

The development in the synthesis and self‐assembly of patchy nanoparticles has resulted in the creation of complex hierarchical structures. Co‐assembly of polymeric nanoparticles and protein molecules combines the advantages of polymeric materials and biomolecules, and will produce new functional materials. Co‐assembly of positively charged patchy micelles and negatively charged bovine serum albumin (BSA) molecules is investigated. The patchy micelles, which were synthesized using block copolymer brushes as templates, leads to co‐assembly with protein molecules into vesicular structures. The average size of the assembled structures can be controlled by the molar ratio of BSA to patchy micelles. The assembled structures are dissociated in the presence of trypsin. The protein–polymer hybrid vesicles could find potential applications in medicine.     

Loading and in vitro controlled release of indomethacin using amphiphilic cholesteryl-bearing carboxymethylcellulose derivatives

Amphiphilic CCMCs were synthesized under mild conditions and their chemical structures were characterized by FT-IR and 1H NMR spectroscopy. Fluorescence analysis showed that CCMCs could self-associate to form polymeric micelles in aqueous solution. IND was encapsulated during the formation of CCMC micelles and its in vitro release properties were investigated. The loading capacity was more than 50% and the loaded IND was slowly and steadily released into the medium over a period of 8 h. The CCMC micelles showed pH-responsive behavior during the drug-loading and release processes. CCMC is promising as a potential delivery system for the controlled release of IND with a pH-responsive property.     

Macromolecular assembly: from irregular aggregates to regular nanostructures

Based on our long-term research on interpolymer complexation due to hydrogen bonding, we proposed several novel self-assembly approaches to polymeric micelles with regular structures. Differing from micelles of block and graft copolymers, our micelles don't have any chemical bonds between the core and shell. In addition, some of these approaches have been proved to be effective to fabricate hollow aggregates.     

Novel amphiphilic macromolecules and their in vitro characterization as stabilized micellar drug delivery systems

A series of amphiphilic macromolecules, amphiphilic scorpion-like macromolecules (AScMs) and amphiphilic star-like macromolecules (ASMs), were evaluated as potential drug delivery systems for intravenous administration. AScMs aggregate to form polymeric micelles; whereas the ASMs have a covalently bound core structure and behave as unimolecular micelles. Four structurally different AScMs and two ASMs were selected for further evaluation focusing on micellar stability and biocompatibility. AScMs were determined to have extremely low cmc values, indicating excellent thermodynamic stability compared to other polymeric micelle systems. Particle sizes of the AScM polymeric micelles and ASM unimolecular micelles were between 10 and 20 nm, and remained constant for up to 3 weeks storages as aqueous solutions at room temperature (approximately 23 degrees C) and 37 degrees C. The dissociation kinetics of the AScM polymeric micelles were slowed relative to small molecule surfactant micelles, again indicating enhanced kinetic stability. With respect to hemolytic activity, AScMs with longer acyl chains were hemolytic; whereas the ASMs had minimal hemolytic activity due to the covalently bound structure. Both ASM unimolecular micelles and AScM polymeric micelles have excellent micellar stability, but the ASMs are more suitable as injectable drug delivery systems due to their low hemolytic activity.     

Preparation and self-assembly of pH-sensitive amphiphilic comb-shaped copolymer containing long fluorinated side chains

Novel pH-sensitive amphiphilic comb-shaped copolymers containing long fluorinated side chains, which combined the characteristics of pH-sensitivity from pendent tertiary amine groups, unique hydrophobic and fluorophobic characteristic from the fluorinated moieties and hydrophilicity from the poly (ethylene glycol) segments, were designed and synthesized via radical polymerizaion of 2-(Dimethylamino) ethyl methacrylate (DMAEMA), poly (ethylene glycol) methyl ether methacrylate (PEGMA) and homemade fluorinated macromonomer (PHFBMA-GMA). The physicochemical properties of polymeric micelles prepared therefrom were investigated. The chemical structures of the copolymers were characterized by GPC, FTIR and ¹H-NMR. The critical micelle concentrations (CMC) of the copolymers in different pH (5.0 and 7.4) were determined by fluorescence spectroscopy. Larger CMCs could be obtained in lower pH since the pronation of DMAEMA moieties enhanced the hydrophilicity. With increasing the amount, as well as the molecular weight, of PHFBMA-GMA, CMC decreased significantly. As pH decreased, particle size, as well as zeta potential of the polymeric micelles increased significantly, indicating significant pH-sensitivity of the polymeric micelles. Furthermore, larger polymeric micelles were obtained with larger amount, as well as higher molecular weight, of PHFBMA-GMA. Transmission electron microscopy (TEM) showed that the morphological shapes of the copolymers performed spherical micelles. The cytotoxicity test showed that the comb-shaped copolymers performed extremely low cytotoxicity. The pH-sensitive polymeric micelles prepared from the amphiphilic comb-shaped copolymers containing long fluorinated side chains could be potential candidates for nanotanks for hydrophobic or fluorophobic molecules and drug carriers and the facile preparation might fit for large scale industrialization.     

Synthesis,self-assembly,and pH-responsive drug release of PHMEMA-PEG-PHMEMA ABA triblock copolymers

Abstract

A series of tertiary amine containing PHMEMA-PEG-PHMEMA ABA triblock copolymers were synthesized by atom transfer radical polymerization (ATRP) using bromine-capped poly(ethylene glycol) (Br-PEG-Br) and 2-(hexamethyleneimino)ethyl methacrylate (HMEMA) as macro-initiator and monomers, respectively. The chemical structures and molecular weights of triblock copolymers were characterized by ¹H NMR and gel permeation chromatography (GPC). The self-assembly behaviors of copolymers in different pH conditions were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Triblock copolymers self-assembled into micelles in water (pH 7.4) and the micelles disassembled at acidic pH (pH 5.0). Anticancer drug doxorubicin (DOX) was used as a drug model and physically encapsulated into polymeric micelles. The drug release of DOX-loaded polymeric micelles was pH-responsive; the drug-loaded micelles that had higher contents of tertiary amine in polymer pendant groups showed faster release speed. In addition, the drug-loaded micelles showed excellent inhibition efficacy against HeLa cells in vitro.     

Hierarchical Self-Assembled Photo-Responsive Tubisomes from a Cyclic Peptide-Bridged Amphiphilic Block Copolymer

Typically, the morphologies of the self-assembled nanostructures from block copolymers are limited to spherical micelles, wormlike micelles and vesicles. Now, a new generation of materials with unique shape and structures, cylindrical soft matter particles (tubisomes), are obtained from the hierarchical self-assembly of cyclic peptide-bridged amphiphilic diblock copolymers. The capacity of obtained photo-responsive tubisomes as potential drug carriers is evaluated. The supramolecular tubisomes pave an alternative way for fabricating polymeric tubular structures, and will expand the toolbox for the rational design of functional hierarchical nanostructures.     

CMC系列高分子表面活性剂的胶束形态

高分子表面活性剂分子量高 ,分子中兼具亲水和疏水链段 ,在选择性溶剂水中同小分子表面活性剂一样 ,可形成疏水链段为核心、亲水链段为外壳的胶束结构 ,但高分子量又使其表现出许多不同于低分子表面活性剂的形态特征 ,如胶束的多种形态、尺寸分布多分散性等等 ,而这些形态特征对高分子表面活性剂的界面活性、增粘、乳化等性能有决定性的影响．结构规整的嵌段或接枝共聚物在选择性溶剂中的分子聚集形态已有研究 ［１,２］,亲水亲油性的高分子表面活性剂在水溶液中由于结构复杂、水溶液中氢键作用及静电作用力等因素造成的困难 ,因而研究较少…