APEG/PS/ODMA两亲性梳型聚合物的合成与溶液性质

采用自由基聚合方法制备多种亲水基含量不同的两亲性梳型聚合物烯丙基聚乙二醇/聚乙烯/马来酸单十八酰胺(APEG/PS/ODMA)。利用核磁共振、红外光谱等测试产物结构,凝胶渗透色谱测试聚合物相对分子质量及其分布,乌氏黏度计检测聚合物黏度变化规律,动态光散射测试胶束粒子尺寸,透射电镜照片确认胶束粒子形态。结果表明,在亲水基含量为单体总量40%～55%时,聚合物相对分子质量随亲水基含量增加而增大,且相对分子质量分布均匀;不同亲水基含量的聚合物在水中形成临界胶束浓度均为0. 3 g/L;胶束粒径尺寸随聚合物浓度增加而增大,胶束分布不均匀;胶束粒子是核壳结构的球形胶束。     

Cellulose-g-PCL两亲性聚合物的合成表征及自组装行为

在离子液体1-丁基-3-甲基咪唑氯盐(Bmim Cl)中,通过羟基与单体ε-己内酯之间的开环接枝聚合反应(ROP),制备Cellulose-g-PCL两亲性衍生物,利用红外光谱、核磁共振、X射线衍射、热重分析等技术对其结构和性能进行表征。通过改变催化剂种类和单体用量调节聚合物分子内疏水/疏水基团比例。荧光探针、透射电镜和动态光散射分析结果表明,Cellulose-g-PCL聚合物在水相中可自组装形成均一球形胶束,粒径位于纳米尺度范围内(30~130 nm),聚合物临界胶束浓度(CMC)较低(9.42~83.43μg/m L)。胶束粒径和CMC值均随聚己内酯的接枝率增加而降低。     

双重敏感性两亲性聚己内酯混合胶束的合成

合成了两亲性嵌段共聚物聚己内酯(ε-己内酯)-b-聚甲基丙烯酸二乙胺基乙酯和聚乙二醇-二硫键-聚己内酯,用核磁氢谱和凝胶渗透色谱对聚合物的结构及分子量进行了表征。用溶剂挥发法制备了聚合物胶束,用动态光散射以及扫描电镜对胶束结构及性质进行了表征。结果显示,两种聚合物自身可以形成胶束,也可以形成混合胶束;形成的混合胶束粒径在pH小于5.5或pH大于6.5时基本保持稳定,且前者稍大于后者,而在10mmol/L的二硫苏糖醇(DTT)的还原条件下,胶束发生破坏并产生团聚,体现了混合胶束的pH敏感性和还原敏感性,期望能够作为新的药物载体。     

一种pH响应型Y形两亲聚合物的合成表征及药物释放性能EI北大核心CSCD

乙氧基乙基缩水甘油醚作为聚合单体,采用阴离子活性聚合(AROP)的方法合成了一种Y形两亲性聚合物聚乙二醇-聚乙氧基乙基缩水甘油醚(PEG-b-PEEGE),并在支点位置引入对弱酸敏感的缩酮结构。采用核磁共振和凝胶渗透色谱对其结构和相对分子质量进行表征。通过旋蒸法制备聚合物胶束,采用透射电镜和动态光散射对胶束的形貌及尺寸进行表征,结果显示聚合物胶束呈球形,平均粒径为88.36 nm。以阿霉素为模型药物考察聚合物的载药及在不同pH环境下的释放行为,结果表明这种缩酮结构的两亲性聚合物具有良好的pH响应性释放能力,即在酸性条件下(pH 4.0)的释放速率比生理pH环境下明显加快。     

基于聚乳酸两亲性共聚物的立构复合胶束与物理凝胶的研究进展

两亲性共聚物在水溶液中可形成胶束、物理凝胶等多层次自组装结构,疏水链段的结晶和立构复合是影响其胶束、物理凝胶形成的过程、结构与性能的重要因素。聚乳酸(PLA)是一种典型的生物基/生物可降解高分子,其2种对映体聚左旋乳酸(PLLA)与聚右旋乳酸(PDLA)之间可形成立构复合结晶。由于立构复合结晶中较强的链间相互作用,含PLLA和PDLA疏水链段的两亲性共聚物水溶液混合后,可形成立构复合胶束与物理凝胶,这为生物可降解、生物相容的胶束与物理凝胶材料的制备与性能调控提供了一种新方法,近年来该领域备受关注。文中介绍了基于PLA两亲性共聚物的立构复合胶束与物理凝胶的制备和性能,并从聚合物链拓扑结构设计出发,详细综述了近年来PLA立构复合胶束与物理凝胶的研究进展,以及聚合物相对分子质量、浓度、共聚组成、温度等因素对立构复合胶束和凝胶结构与性能的影响。     

一种pH响应型Y形两亲聚合物的合成表征及药物释放性能

乙氧基乙基缩水甘油醚作为聚合单体,采用阴离子活性聚合(AROP)的方法合成了一种Y形两亲性聚合物聚乙二醇-聚乙氧基乙基缩水甘油醚(PEG-b-PEEGE),并在支点位置引入对弱酸敏感的缩酮结构。采用核磁共振和凝胶渗透色谱对其结构和相对分子质量进行表征。通过旋蒸法制备聚合物胶束,采用透射电镜和动态光散射对胶束的形貌及尺寸进行表征,结果显示聚合物胶束呈球形,平均粒径为88.36 nm。以阿霉素为模型药物考察聚合物的载药及在不同pH环境下的释放行为,结果表明这种缩酮结构的两亲性聚合物具有良好的pH响应性释放能力,即在酸性条件下(pH 4.0)的释放速率比生理pH环境下明显加快。     

两亲性接枝共聚物P(MMA-co-GMA)-g-mPEG的合成

借助原子转移自由基聚合(ATRP)技术和环氧功能基团的大分子后修饰反应合成具有梳型结构的两亲性接枝共聚物P(MMA-co-GMA)-g-mPEG)。首先,采用ATRP方法,以2-溴代丙酸乙酯(EPN-Br)为引发剂,氯化亚铜(CuCl)/2,2′-联二吡啶(bpy)为催化体系,引发甲基丙烯酸甲酯(MMA)和甲基丙烯酸环氧丙酯(GMA)无规共聚,合成二元无规共聚物P(MMA-co-GMA);然后,在催化剂BF3/Et2O的作用下,无规共聚物P(MMA-co-GMA)的环氧基团开环,与单甲氧基封端的聚乙二醇(mPEG)发生接枝(grafting-onto)反应,获得具有梳型结构的两亲性接枝共聚物P(MMA-coGMA)-g-mPEG。采用红外光谱(IR)、凝胶色谱(GPC)、核磁共振氢谱(1 H-NMR)及差示扫描量热仪(DSC)等技术对聚合物的结构和性能进行表征。研究的特点是无规共聚物的合成可控性好,后修饰反应获得两亲性接枝共聚物的效率高,为研究接枝共聚物结构与性能的关系提供了物质依据。     

两亲性梳型超塑化剂的制备与表征

为了研究疏水长侧链对梳型超塑化剂分散性能的影响,采用水溶液自由基共聚方法,以过硫酸铵为引发剂合成了两亲性梳型聚甲基丙烯酸十二酯-异戊烯醇聚氧乙烯醚-马来酸酐三元共聚物(APC)。利用傅里叶变换红外光谱、核磁共振光谱和凝胶渗透色谱对共聚物的分子结构和相对分子质量进行了表征,并用动态光散射(DLS)和透射电子显微镜(TEM)对共聚物的构象及尺寸进行了表征。分子结构及相对分子质量测试结果显示,3种单体很好地发生了共聚反应,样品的重均和数均相对分子质量分别为50625和10173,相对分子质量分布指数为4.97。DLS和TEM测试结果显示,疏水烷基酯长侧链的引入使梳型共聚物在水泥孔隙溶液中自组装形成100 nm以上的胶束,TEM观察胶束呈球形并相互胶结成团聚体,增大了共聚物的流体力学半径和溶剂化层厚度,改善了减水剂的分散性能。     

温度敏感型两亲性嵌段聚合物的合成与表征

以二硫代苯甲酸(4-氰基戊酸)酯为链转移剂,苯乙烯为亲油单体,乙烯基己内酰胺为亲水性单体,通过RAFT技术合成了两亲性嵌段共聚物。由FT-IR、1H-NM R和13C-NM R确定了共聚物的结构,分子量及其分布通过GPC测定,分别为14600 g/m o l和1.21。粒度测定结果发现,两亲性共聚物可在水溶液中自组装成胶束,其粒径约为150 nm,TEM观察胶束呈球形,其尺寸证实了粒度测定结果。由胶束溶液在不同温度下的透光率证实了胶束的温度敏感性。通过在不同温度测定胶束粒径发现其随着温度的升高而增加,并且多分散指数也在增加,这是由胶束的凝聚造成的。     

N-烷基取代丙烯酰胺类三嵌段共聚物的温敏性聚集行为

利用原子力显微镜对两种温敏性不同嵌段序列N-异丙基丙烯酰胺(NIPAM)与N,N-二甲基丙烯酰胺(DMA)的三嵌段共聚物P(DMA32-b-NIPAM166-b-DMA32)、P(NIPAM65-b-DMA30-b-NIPAM53)溶液的聚集形貌进行了研究,前者在15℃不同质量浓度均以单分子线团聚集,50℃时1.0 g/L形成胶束间大聚集体,直径约为3.3μm,降低质量浓度至0.1g/L及以下则形成多分子胶束,但无胶束间聚集体形成。后者在15℃、50℃,1.0 g/L质量浓度均形成胶束间聚集体,降低质量浓度至0.1 g/L、0.01 g/L则只形成多分子胶束,胶束直径约60 nm~90 nm。     

Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for drug delivery

A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) segment was designed and synthesized. The structure of the copolymer was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The copolymer may self-assemble into micelles in water, with the hydrophobic POA segments at the cores of micelles and the hydrophilic PNIPAAm segments as the outer shells. The resulting micelles demonstrate temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow size range of approximately 10-30 nm. A study of controlled release reveals that the self-assembled micelles have great potential as drug carriers.     

Thermal-sensitive PBMA-b-PNIPAAm amphiphilic block copolymers brushes and their assembling micelles

Brush-like block copolymers with poly(t-butyl methacrylate) (PBMA) and poly(N-ispropylacrylamide) (PNIPAAm) as side arms, PBMA-b-PNIPAAm, were designed and synthesized via a simple free radical polymerization route. The chemical structure of these polymer brushes was characterized and determined by nuclear magnetic resonance (1H NMR), and Fourier transform infrared spectrometry (FT-IR). The micellar formation by these polymer brushes in aqueous solutions were detected by a surface tension technique, and the critical micelle concentration (CMC) ranged from 1.53 to 8.06 mg L(-1). The morphology and geometry of polymer micelles were investigated by transmission electron microscope (TEM) and dynamic light scattering (DLS). The polymer micelles assume the regularly-spherical core-shell structure with well-dispersed individual nanoparticles, and the particle size was in the range from 36 to 93 nm. The PNIPAAm segments exhibited a thermoreversible phase transition, so the resulting block polymer brushes were temperature-sensitive and the low critical solution temperature (LCST) was determined by UV-vis spectrometer at about 28.82-29.40 degrees C. The characteristic parameters of the polymer micelles such as CMC, micellar size and LCST values were affected by their compositional ratios and the length of hydrophilic or hydrophobic chains. The self-assembled micelles are expected to be used in specific biomedical fields as a candidate of drug controlled release carrier.     

两亲性三嵌段聚合物的合成与表征及分子自组装行为

以三硫代碳酸(α,α′-二甲基α-″-乙酸)酯为链转移剂,苯乙烯为第一单体,通过RAFT聚合技术合成出大分子链转移剂(PS-CTA);以甲基丙烯酸-N,N-二甲氨基乙酯为第二共聚单体合成出具有不同链长的三嵌段聚合物。GPC对PS-CTA的表征表明:PS-CTA的分子量分别为2100、3500和5000g/m o l,分子量分布约为1.03;NM R表征确定了三嵌段共聚物的结构。三嵌段共聚物在选择性溶剂中可自组装成胶束,通过TEM观察发现胶束呈球形;并且胶束的尺寸随嵌段共聚物分子量的增加而增加。     

Synthesis and characterization of three novel amphiphilic dextran self-assembled micelles as potential drug delivery system

Three types of amphiphilic dextran derivatives were synthesized via the connection of different diamine compounds between the carboxyl group of stearic acid (SA) and aldehyde group of oxidized dextran. These three amphiphilic dextran derivatives self-assemble to form polymer micelles in aqueous medium. The critical micelle concentration depended on the graft ratio of SA, which ranged from 0.0700 to 0.158 mg mL^?1. These three amphiphilic dextran micelles can form typical core–shell structures of various sizes. Curcumin (Cur) was used as a model drug, and all amphiphilic micelle dextran derivatives had excellent drug loading capacity and drug encapsulation efficiency. The in vitro drug release from amphiphilic dextran derivatives/Cur micelles could be prolonged by adjusting the type of diamine compounds and composition of Cur content. These results show the superior properties of polymer micelles and suggest that these micelles are promising carriers for drug delivery systems.     

Folate-conjugated polymer micelles for active targeting to cancer cells: preparation, in vitro evaluation of targeting ability and cytotoxicity

To obtain an active-targeting carrier to cancer cells, folate-conjugated stearic acid grafted chitosan oligosaccharide (Fa-CSOSA) was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The substitution degree is 22.1%. The critical micelle concentrations (CMCs) of Fa-CSOSA were 0.017 and 0.0074?mg?ml(-1) in distilled water and PBS (pH?7.4), respectively. The average volume size range of Fa-CSOSA micelles was 60-120?nm. The targeting ability of Fa-CSOSA micelles was investigated against two kinds of cell lines (A549 and Hela), which have different amounts of folate receptors in their surface. The results indicated that Fa-CSOSA micelles presented a targeting ability to the cells (Hela) with a higher expression of folate receptor during a short-time incubation (<6?h). As incubation proceeded, the special spatial structure of the micelles gradually plays a main role in cellular internalization of the micelles. Good internalization of the micelles into both Hela and A549 cells was shown. Then, paclitaxel (PTX) was encapsulated into the micelles, and the content of PTX in the micelles was about 4.8% (w/w). The average volume size range of PTX-loaded micelles was 150-340?nm. Furthermore, the anti-tumor efficacy in vitro was investigated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method. The IC(50) of Taxol (a clinical formulation containing PTX) on A549 and Hela cells was 7.0 and 11.0?μg?ml(-1), respectively. The cytotoxicity of PTX-loaded micelles was improved sharply (IC(50) on A549: 0.32?μg?ml(-1); IC(50) on Hela: 0.268?μg?ml(-1)). This is attributed to the increased intracellular delivery of the drug. The Fa-CSOSA micelles that are presented may be a promising active-targeting carrier candidate via folate mediation.     

Electrochemical performance of steel in cement extract and bulk matrix properties of cement paste in the presence of Pluronic 123 micelles

The influence of Pluronic P123 (PEO₂₀-PPO₇₀-PEO₂₀) non-stabilized micelles (of 10 nm size) on the corrosion behavior of low-carbon steel in cement extract was studied, using electrochemical impedance spectroscopy (EIS) and potentio-dynamic polarization (PDP). Mercury intrusion porosimetry (MIP) was employed to derive the impact of admixed P123 micelles on porosity and pore-size distribution of cement paste. As far as steel corrosion resistance is concerned, a positive effect was observed, initially denoted to the presence of the polymer itself, rather than the presence of micelles. Further, the P123 micelles were found to result in increased corrosion resistance in the presence of 1 % and 3.5 % NaCl in the alkaline environment of cement extract. There was no significant influence on porosity and pore size distribution of the admixed in cement paste P123 micelles. The observed phenomena are related to self-assembly of the micelles only within higher ionic strength and the presence of chloride, in which case the critical micelle concentration is reduced. At micelles concentration of 0.024 g/l for the chloride-free cement extract (and the solid cement paste specimens, respectively), the medium actually contain unimers that have minimal impact on electrochemical performance and/or microstructural properties. In contrast, with increased ionic strength of the medium (1?3.5 % NaCl and altered ion concentrations resulting from the anodic/cathodic reactions within steel corrosion), the positive effect of 0.024 g/l micelles (and higher of 0.072 g/l) is more pronounced, i.e., increased corrosion resistance and anodic control with external polarization was observed.     

温度/pH敏感性荧光胶束的制备及性能研究

通过溴乙酰溴与9-氨基吖啶(9-AA)的酰胺化反应,合成了带有2个活性溴原子的新型荧光性引发剂9-AA-Br。核磁共振氢谱(1 H-NMR)测定表明其结构明确。以氯化亚铜(CuCl)/四氮杂十四员大环冠醚(Me6[14]aneN4)为催化体系,由9-AA-Br引发N-异丙基丙烯酰胺(NIPAAm)进行原子转移自由基聚合(ATRP),成功合成了结构明确、分子量可控的双臂型PNIPAAm大分子荧光探针,由紫外分光光度计测得其最低临界溶解温度(LCST)在32℃左右,且随着溶液浓度及聚合物分子量的增加而降低。温度低于LCST时,PNIPAAm大分子荧光探针在溶液中能进行自组装形成胶束,由透射电镜(TEM)观察表明,胶束的大小在500nm左右,该聚合物胶束还具有pH敏感性,在碱性条件下随着pH的增大,荧光发射峰变强。     

直链淀粉-鹅去氧胆酸接枝聚合物的合成及其自组装行为

使用1-乙基-3-(3－二甲基氨丙基)-碳化二亚胺(EDC)/N-羟基琥珀酰亚胺(NHS)交联剂合成一种直链淀粉接枝鹅去氧胆酸聚合物(Amylose–chenodeoxycholic acid conjugates, AMY-CDCA),并用傅里叶变换红外光谱(FTIR)、核磁共振氢谱(¹H NMR)和紫外光谱法对其进行了表征。结果表明,CDCA已经成功地接枝到直链淀粉骨架上,接枝度为138.15/100个葡萄糖单元。可用透析法将AMY-CDCA聚合物制备成球形并具有核壳结构的胶束,其平均粒径为224 nm,多分散指数为0.110。使用疏水性荧光探针芘和尼罗红研究了胶束的组装行为。结果表明,聚合物的临界胶束浓度(CMC)为2.8×10^-3 mg/mL,其疏水核心对尼罗红有增溶作用。     

环糊精二聚体与双支化两亲聚合物包合体系的构筑

将实验室自制的环糊精二聚体(66βCDsu)与双支化两亲聚合物(P(AM/BHAM/NaA))加入到水溶液中,发生包合作用构筑包合体系。研究该体系的增黏及溶液流变学特性,并采用荧光光谱仪、扫描电镜及差示扫描量热仪等研究包合体在溶液中的包合机制及结构形态。结果表明,由于P(AM/BHAM/NaA)中1个疏水单体中存在2个疏水基团(正十六烷基和苄基),因此环糊精与疏水单体BHAM最大摩尔包合比为2∶1,完全包合后溶液中没有游离态疏水基团,因此溶液不存在临界聚集浓度(CAC)。当环糊精与BHAM摩尔包合比为1∶1,体系存在明显的CAC,这是由于环糊精首先包合双支化疏水单体中的苄基形成包合体,而正十六烷基依然存在于水溶液中。当P(AM/BHAM/NaA)浓度为800mg/L时,该体系中存在2种聚集方式,一种是疏水基团的疏水缔合;另一种是包合作用。通过扫描电镜证明了不同体系的微观聚集形态。