ABC block copolymer as “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs

Amphiphilic triblock copolymer of poly(ethylene glycol)-block-poly(dimethylaminoethyl methacrylate)-block-poly(ε-caprolatone) (PEG-PDMA-PCL) was synthesized using a one-pot sequential oxyanionic polymerization of DMA and ε-CL, associated with a PEG-O⁻K⁺ macroinitiator. The pH-responsive micellization behavior of the copolymer was studied using dynamic light scattering (DLS), steady-state fluorescence and TEM techniques. The anti-cancer drug of doxorubicin (DOX) was chosen as a model drug to investigate the potential application of this triblock copolymer in drug controlled release. The results indicated the important roles of the PCL block for drug loading, the PDMA block for pH-responsive release, and PEG block for good bio-affinity. Cell cytotoxicity tests showed that the DOX-loaded PEG-PDMA-PCL micelles were pharmaceutically active to suppress the growth of SKOV-3 cells. This novel stimuli-responsive block copolymer is an attractive candidate as the “smart” pH-responsive carrier for intracellular delivery of hydrophobic drugs.     

两亲嵌段共聚物的合成及其自组装研究进展

作者介绍了两亲嵌段共聚物的活性阴离子聚合、基团转移聚合、开环歧化聚合、活性阳离子聚合、活性／可控自由基聚合、缩聚法、嵌段共聚物化学改性法等合成方法,并对其自组装形成聚合物纳米胶束的制备方法、形成机理以及在药物控制释放领域的应用进行了综述,并对其未来发展趋势进行了展望。     

Influence of chemical structure on enzymatic degradation of single crystals of PCL-b-PEO amphiphilic block copolymer

Solution-grown lamellar single crystals of PCL homopolymer and amphiphilic block copolymers of PCL-b-PEO-b-PCL and PCL-b-PEO-FG (functional groups FG = NH₂, OCH₃) were prepared by self-seeding procedures. The crystal structure and morphology of these single crystals were mainly studied by means of transmission electron microscopy (TEM) and atomic force microscopy (AFM). The results indicated that the shorter PEO blocks as well as the functional groups bonded to the end of PEO block are in an amorphous state and located in the surface of single crystals. The enzymatic degradation of single crystals prepared from these homopolymer and amphiphilic block copolymers has been well-studied to demonstrate the effects of chemical structure on degradation behavior. The single crystals showed similar morphologies before enzymatic degradation but very different surface character after enzymatic degradation. Such differences resulted from the PEO block and functional end groups. The results of this work indicated the important role of chemical structure in determining biodegradation behavior.     

Synthesis and micelle behavior of (PNIPAm-PtBA-PNIPAm)m amphiphilic multiblock copolymer

A linear amphiphilic multiblock copolymer (PNIPAm-PtBA-PNIPAm)_m was successfully synthesized by a two-step reversible addition-fragmentation transfer (RAFT) polymerization in the presence of a cyclic trithiocarbonate as RAFT agent. The micelle behavior of (PNIPAm-PtBA-PNIPAm)_m multiblock copolymer in aqueous solution was then investigated by means of normal TEM, cryo-TEM, static and dynamic light scattering. The morphology, size, and size distribution of (PNIPAm-PtBA-PNIPAm)_m micelles were found to be dependent on the initial concentration of multiblock copolymer in THF. Spherical micelles, associated aggregates of spherical micelles, cage-like micelles, layered structures, and vesicular micelles were experimentally observed, which were in good agreement with the prediction of theory and simulations on linear amphiphilic multiblock copolymer in selective solvent. The (PNIPAm-PtBA-PNIPAm)_m micelles also exhibit thermo-sensitive behavior in aqueous solution because of the PNIPAm blocks.     

Aqueous lubricating properties of charged (ABC) and neutral (ABA) triblock copolymer chains

Application of charged polymer chains as additives for lubricating neutral surfaces in aqueous environment, especially via polymer physisorption, is generally impeded by the electrostatic repulsion between adjacent polymers on the surface. In this study, we have investigated the adsorption and aqueous lubricating properties of an amphiphilic triblock copolymer, comprised of a neutral poly(ethylene glycol) (PEG) block, a hydrophobic poly(2-methoxyethyl acrylate) (PMEA) block, and a charged poly(methacrylic acid) (PMAA) block, namely PEG-b-PMEA-b-PMAA. After adsorption onto a nonpolar hydrophobic surface from aqueous solution, an equal and homogeneous mixture of neutral PEG and charged PMAA chains is formed on the surface, with an adsorbed polymer mass comparable to its fully neutral counterpart, PEG-b-PMEA-b-PEG. The lubricity of PEG-b-PMEA-b-PMAA showed significant improvement compared to fully charged polymer chains, e.g. poly(acrylic acid)-block-poly(2-methoxyethyl acrylate) (PAA-b-PMEA), which is attributed to dilution of charged moieties on the surface and subsequent improvement of the lubricating film stability.     

Synthesis and characterization of biodegradable and biocompatible amphiphilic block copolymers bearing pendant amino acid residues

Polylactide (PLA)-based biodegradable and biocompatible amphiphilic block copolymers bearing pendant amino acid residues were synthesized through a relatively easy and efficient way. The composition and structure of these copolymers were characterized by gel permeation chromatography (GPC) and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy. The self-assembly behavior of the copolymers was investigated by fluorescence (FL), dynamic light scattering (DLS), and transmission electron microscope (TEM). It was shown that aggregates less than 100 nm in average size were formed by these copolymers, which changed from micelles to vesicles with the variation of the block length. In addition, the in vitro cytotoxicity of these copolymers was determined and compared with that of PEO-b-PLA in the presence of Bel-7402 cells. The result suggested that the block copolymers PAGE/cys-b-PLA exhibited better biocompatibility. Therefore, these PLA-based copolymers are expected to find promising applications in drug delivery or tissue engineering.     

氢化苯乙烯-丁二烯-苯乙烯嵌段共聚物研究进展

概述了氢化苯乙烯-丁二烯-苯乙烯嵌段共聚物(SEBS)国内外生产状况,介绍了SEBS生产工艺技术及其加氢催化剂的开发进展,提出应加强SEBS的改性及应用技术开发,在国内尽快实现SEBS的规模化工业生产。     

丁苯嵌段共聚物合成中大分子的形成及控制方法

本文研究了以正丁基锂为引发剂，在环己烷中合成丁二烯-苯乙烯嵌段共聚物树脂(SBS)时影响SBS物理机械性能的大分子和凝胶产物的形成机理，阐明了单体浓度和聚合反应温度是主要产生原因。为了降低SBS中的大分子和凝胶产物，提出较理想的条件和应采取的控制方法。     

Long-tailed spherical aggregates formed from ABA triblock copolymer by changing the properties of selective solvent

A convenient method of tuning aggregate morphologies from amphiphilic block copolymer by adding second selective solvent is introduced in this paper. Some novel aggregate morphologies, i.e. hierarchical vesicles (and compound spherical micelles) with one or more tails, were formed by introducing a second selective solvent for core-forming blocks into the poly(4-vinyl pyridine)-b-polystyrene-b-poly(4-vinyl pyridine) ABA amphiphilic block copolymer/co-solvent/water systems. Addition of selective solvent (toluene) for core-forming blocks (PS blocks) has significant effect on the aggregate morphologies from the amphiphilic triblock copolymer. The aggregate morphologies changed from spheres to rods, long tailed solid large compound spheres, and to long tailed hierarchical vesicles by adding 0.5, 10 and 30 wt% of toluene to the organic solvent, respectively. There exists an aggregate morphological transition of the long tailed hierarchical vesicles to long tailed solid spheres by decreasing the content of toluene in the organic solvent mixture. The tails disappeared, and irregular vesicular and spherical structures were formed when the toluene content was 20 wt%. The toluene addition is expected to increase the stretching of the core-forming blocks (PS), and to modify the interfacial tension of core-corona interface, which are the main reasons for the aggregate morphology transition. To the best of our knowledge, these tailed vesicles and spherical morphologies have not been found in block copolymer aggregates system up to now.     

PBT-PTMG嵌段共聚酯的研究

对以对苯二甲酸二甲酯、1,4-丁二醇和四氢呋喃聚醚二元醇为原料,钛酸四丁酯为催化剂制备PBT—PTMG嵌段共聚酯的工艺方法进行了研究。制备了软硬段比不同的PBT—PTMG嵌段共聚酯切片,并对其性能进行了表征。其结果显示,PBT—PTMG嵌段共聚酯的密度和硬度都随PBT含量的增大而增大,吸水率随聚醚含量增大而增大;调节PBT-PTMG嵌段共聚酯的组成可以得到具有不同力学性能的产物,且具有良好韧性。     

Honeycomb structured porous films from amphiphilic block copolymers prepared via RAFT polymerization

The synthesis of polystyrene-block-poly(N,N-dimethylacrylamide) (PS-b-PDMA) via RAFT polymerization was investigated in detail. Two different RAFT agents - benzyl dithiobenzoate and 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, were employed to prepare polystyrene macroRAFT agents with molecular weights varying between 3000 g mol⁻¹ and 62,000 g mol⁻¹ and polydispersities between 1.1 and 1.4. Chain extensions with N,N-dimethylacrylamide (DMA) were carried out using a constant monomer to RAFT agent concentration ([DMA]/[RAFT] = 500), to compare the rate of polymerization in dependency of the polystyrene chain length. A decreasing rate of polymerization with increasing block length was observed. Depending on the sizes of the first block and type of RAFT agents used, chain extension polymerization with DMA was found to be incomplete, leading to significant low molecular weight tailing in the GPC analyses. Block copolymers prepared using 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, followed the expected molecular weight evolutions with polydispersity indices of 1.2-1.4. In contrast, block copolymers using benzyl dithiobenzoate clearly showed bimodal molecular weight distributions, especially when the longest PS macroRAFT agent with a molecular weight of 38,000 g mol⁻¹ was employed. These amphiphilic block copolymers were used to fabricate honeycomb structured porous films using the breath figure technique. The regularity of the film was considerably influenced by the humidity of the environment, which could be controlled by the rate of the airflow or the humidity in the casting chamber. The interaction between the hydrophilic block copolymer and the humidity was found responsible for the delicate equilibrium during the casting process, which prevented high pores regularity at very low (below 50%) and at elevated (above 80%) humidity. The interactions of the hydrophilic block with the humidity were observed to superimpose an additional nano-scaled order onto the hexagonal micron-sized porous array. Pores, which are created by encapsulation of water droplets, were found to be more hydrophilic than the surface. Confocal microscopy studies were employed to locate hydrophilic blocks within the film using a fluorescence labeled PDMA polymer.     

生物可降解两亲性嵌段共聚物胶束的制备及其对叶酸的控制释放

以甲氧基聚乙二醇(mPEG)为引发剂,在辛酸亚锡催化下引发ε-环己内酯(CL)开环聚合,合成了聚乙二醇-聚己内酯两亲性嵌段共聚物(mPEG-PCL)。通过FTIR、1H-NMR及GPC等表征手段确定了mPEG-PCL的组成及结构。采用芘荧光探针法、透射电镜和动态激光光散射研究了聚合物在水中的自组装行为。结果表明:聚合物在水溶液中能够自组装形成粒径小于100 nm的规则球状胶束,且具有较低的临界胶束浓度(7.35×10-3 g/L);模型药物(叶酸)成功负载于聚合物纳米胶束内,并且能延缓叶酸的释放,其释药速率受载药量和释放介质pH的影响。     

Styrene–butadiene block copolymer with high cis‐1,4 microstructure

The sequential block copolymerization of styrene (St) and butadiene (Bd) was carried out with an activated rare earth catalyst composed of catalyst neodymium tricarboxylate (Nd), cocatalyst Al(i‐Bu)₃ (Al), and chlorinating agent (Cl). The microstructure, composition, and morphology of the copolymer were characterized by FTIR, ¹H NMR, ¹³C NMR, and TEM. The results show that styrene–butadiene diblock copolymer with high cis‐1,4 microstructure of butadiene units (～ 97 mol %) was synthesized. The cis‐selectivity for Bd units was almost independent on the content of styrene units in the copolymer ranging from 18.1 mol % to 29.8 mol %. The phase‐separated morphology of polystyrene (PS) domains of about 40 nm tethered by the elastomeric polybutadiene (PB) segments is observed. The PS‐b‐cis‐PB copolymer could be used as an effective compatilizer for noncompatilized binary PS/cis‐PB blends. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Elongational viscosities of random and block copolymer melts

The influence of random and block copolymerized structures on the uniaxial elongational viscosity was investigated. The investigated random copolymers were poly(ethylene-random-ethyl methacrylate) with comb-branched structure and poly(styrene-random-acrylonitrile) with linear structure. The studied block copolymers were poly(styrene-block-ethylenebutylene-block-styrene) with linear structure. The elongational viscosities of random copolymers showed strain-hardening properties. The strain-hardening property was influenced little by comonomer contents and depended on whether copolymers had linear or branched structures. In contrast, the elongational viscosities of block copolymers gave strain-softening properties. The strain-softening property was not affected by strain rates and block comonomer ratios. The causes of strain-hardening and -softening properties are discussed from relaxation spectrum and damping function based on the Bernstein–Kearsley–Zapas model. The damping functions of linear and branched random copolymers agreed with those of linear and branched homopolymers, respectively. On the other hand, linear block copolymers exhibited stronger damping than linear homopolymers. It was concluded that strain-hardening and -softening properties in the elongational viscosity of random and block copolymerized structures are correlated with their damping functions. © 1998 John Wiley & Sons, Inc. J. Appl. Polym. Sci. 69: 1765–1774, 1998     

Preparation and characterization of amphiphilic block copolymer of polyacrylonitrile‐block‐poly(ethylene oxide)

The synthesis of polyacrylonitrile‐block‐poly(ethylene oxide) (PAN‐b‐PEO) diblock copolymers is conducted by sequential initiation and Ce(IV) redox polymerization using amino‐alcohol as the parent compound. In the first step, amino‐alcohol potassium with a protected amine group initiates the polymerization of ethylene oxide (EO) to yield poly(ethylene oxide) (PEO) with an amine end group (PEO‐NH₂), which is used to synthesize a PAN‐b‐PEO diblock copolymer with Ce(IV) that takes place in the redox initiation system. A PAN‐poly(ethylene glycol)‐PAN (PAN‐PEG‐PAN) triblock copolymer is prepared by the same redox system consisting of ceric ions and PEG in an aqueous medium. The structure of the copolymer is characterized in detail by GPC, IR, ¹H‐NMR, DSC, and X‐ray diffraction. The propagation of the PAN chain is dependent on the molecular weight and concentration of the PEO prepolymer. The crystallization of the PAN and PEO block is discussed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1753–1759, 2003     

用AB嵌段共聚物型分散剂制备色浆

利用以受控自由基聚合技术合成的AB嵌段共聚物型分散剂P12制备了PG7和PR112的色浆,与聚氨酯型分散剂P63进行了性能对比。结果表明,P12制得的色浆平均粒径小于1μm,属于纳米级别;色浆通用型强,在丙烯酸、环氧、聚氨酯、醇酸、硝基等体系中都有较好的相容性,在同等条件下,不影响体系光泽,且可提显著高着色力。     

苯乙烯-异戊二烯-苯乙烯(SIS)嵌段共聚物的镍系催化加氢

Ni(naph) 2 /Al(i-Bu) 3 常温、常压催化SIS加氢的研究结果表明 ,反应只发生在PIp中的不饱和双键上 ,苯环不参与加氢反应 ;实验条件下 ,PIp中的 3,4-链节、1,4-链节具有相同的加氢活性 ;在 5 0℃、0 .1MPa氢压、1.90× 10 -4 mol/g·SIS的Ni用量、Al与Ni的摩尔比为 5时 ,SIS的加氢度可达92 .6 %;陈化后的催化剂显示出较高的加氢活性。     

Theoretical study on morphology of ABCD 4-miktoarm star block copolymer

A real-space implementation of the self-consistent field theory (SCFT) has been used to study the morphologies of ABCD 4-miktoarm star block copolymers. For the sake of numerical tractability, the morphologies and the phase diagrams of ABCD 4-miktoarm star block copolymers are investigated in two dimensions (2D) by varying the volume fractions of the blocks and the interaction parameters. Many interesting and complex morphologies occur and compared with ABCD linear block copolymers; ABCD 4-miktoarm star block copolymers have more regular disciplines. We found that systems with similar components have similar morphologies and at the weaker segregation, the minority components always cannot separate from the other blocks and they easily dissolve to form one phase with other block(s), but with the increase of the segregation degree (large ), the ordered phases can be well separated. With the help of our computational prediction, experimental researchers can work more purposefully and efficiently.     

Optical properties of polystyrene and polyarylate block copolymer and their control by morphology generation

Relationship between phase morphology and optical properties of polystyrene and polyarylate (PS‐PAr) block copolymers synthesized from telechelic polystyrene has been investigated. In the PS‐PAr block copolymers, the PAr domains with higher melt viscosity were dispersed in the PS phase matrix with lower melt viscosity over the wide range of their composition from PS/PAr = 25/75 to 75/25 (wt ratio). The PAr domain size was dependent on the reactive ratio of PAr determined analogously by the mole fraction of the fed telechelic polystyrene. By controlling the mole fraction of the telechelic polystyrene more than 0.016 in synthesizing the PS‐PAr block copolymer, the size of PAr domains could be reduced to the microscopic scale (smaller than 100 nm). Then, the PS‐PAr block copolymers exhibited almost the same transparency as PAr in spite of the large difference in the refractive index between the PS and the PAr phase. Birefringence free condition for the PS‐PAr block copolymers was determined by not only the PS/PAr composition but also the balance in the degree of molecular orientation of these chains. The latter factor suggests that PS and PAr chains undergo inhomogeneous stress and relaxation history during the injection process. By controlling Mn (number average molecular weight) and weight fraction of the fed OH‐PS‐OH around 20 000 and 55 wt %, respectively, in the synthesis of the PS‐PAr block copolymer, the PS‐PAr block copolymer exhibited almost zero birefringence without any sacrifice of transparency. Because in the PS‐PAr block copolymer low birefringence and high transparency can coexist by controlling the adequate feeding condition in the synthesis process, the PS‐PAr block copolymer would be a promising material for optical applications, such as a substrate of optical disks or optical lenses. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 953–961, 2000     

The amphiphilic block copolymers of 2-(dimethylamino)ethyl methacrylate and methyl methacrylate: Synthesis by atom transfer radical polymerization and solution properties

Amphiphilic di- and tri-block copolymers of poly(methyl methacrylate) (PMMA) and poly(2-dimethylamino)ethyl methacrylate (PDMAEMA) have been synthesized by atom transfer radical polymerization (ATRP) at ambient temperature (35 °C) in the environment-friendly solvent, aqueous ethanol (water 16 vol%) using CuCl/o-phenanthroline as the catalyst. The PDMAEMA blocks are contaminated with ethyl methacrylate (EMA) residues to the extent of 1-2 mol% of DMAEMA depending on the length of the PDMAEMA block. The EMA forms through the autocatalyzed ethanolysis of the DMAEMA monomer and undergoes random copolymerization with the latter. The rate of ethanolysis is unexpectedly greater in the aqueous ethanol than in neat ethanol, which has been attributed to the higher polarity of the former than of the latter. In contrast to the ethanolysis no hydrolysis of DMAEMA in the aqueous ethanol medium could be detected for 133 h. The block copolymers form micelles in water. Their solubility and CMC in neutral water have been studied. Dynamic light scattering (DLS) studies reveal that for a fixed degree of polymerization (DP) of the PMMA block the hydrodynamic diameter of the micelles in methanolic water (water 95 vol%) increases at a faster rate with the DP of the PDMAEMA block when it is much greater than that of the PMMA block compared to when it is less than or close to that of the latter.