嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1的合成及其pH和温度敏感性

采用开环聚合法和自由基聚合法合成了生物可降解嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1, 并对其进行了结构表征. 采用荧光分光光度计和激光粒度仪对共聚物溶液临界胶束浓度(CMC)和粒径大小及分布进行了考察, 研究了温度和pH对共聚物胶束形成的影响. 相转变过程研究结果表明, 共聚物溶液具有pH和温度双重敏感性. 共聚物溶液在一定温度和pH条件下可发生溶液-凝胶相转变.     

Lamellar orientation in thin films of symmetric semicrytalline polystyrene-b-poly(ethylene-co-butene) block copolymers: effects of molar mass, temperature of solvent evaporation, and annealing

Orientation of the lamellar microdomains in thin films of three symmetric polystyrene-b-poly(ethylene-co-butylene) block copolymers (S65E155, S156E358, and S199E452) on mica was investigated via atomic force microscopy (AFM), grazing incidence X-ray diffraction (GIXRD) and X-ray photoelectron spectroscopy (XPS). The results show that lamellar orientation in the SxEy block copolymers greatly depends on the molar mass of the block copolymers, the temperature of solvent evaporation, and annealing. The nascent thin film of the low molar mass block copolymer, S65E155, shows a multilayered structure parallel to the mica surface with the PS block at both polymer/mica and polymer/air interfaces, but the high molar mass block copolymers, S156E358 and S199E452, exhibit a structure with lamellar microdomains perpendicular to the mica surface. When the solvent is evaporated at a lower temperature, the crystallization rate is fast and a two-dimensional spherulite structure with the lamellar microdomains perpendicular to the mica surface is observed. Annealing of all the thin films with lamellar microdomains perpendicular to the mica surface leads to morphological transformation into a multilayered structure parallel to the mica surface. In all SxEy thin films on mica, the stems of PE crystals are always perpendicular to the interface between the lamellar PE and PS microdomains. A mechanism is proposed for the formation of different microdomain orientations in the thin films of semicrystalline block copolymers. When the thin film is prepared from a homogeneous solution, microdomains perpendicular to the substrate surface are formed rapidly for strongly segregated block copolymers or at a lower crystallization temperature and kinetically trapped by the strong segregation strength or solidification of crystallization, while for weakly segregated block copolymers or at slower crystallization rate, the orientation of the microdomains is dominated by surface selectivity.     

Micellization and gelation of aqueous solutions of star-shaped PEG-PCL block copolymers consisting of branched 4-arm poly(ethylene glycol) and polycaprolactone blocks

Star-shaped block copolymers consisting of non-toxic poly(ethylene glycol) and biodegradable polycaprolactone ((PEG5K-PCL)₄) were synthesized by ring-opening polymerization of the ε-caprolactone monomer with hydroxyl-terminated 4-armed PEG as initiator. These biodegradable, amphiphilic star block copolymers showed micellization and sol-gel transition behaviors in aqueous solution with varying concentration and temperature. In the dilute aqueous solutions of star block copolymers, micellization behavior occurred over specific concentration. The 1,6-diphenyl-1,3,5-hexatriene (DPH) solubilization method was used to determine the critical micellization concentration (CMC) of star block copolymers. The obtained micelle size increased with increasing hydrophobic PCL block length. In high-concentration solutions, the star block copolymers showed temperature-sensitive sol-gel transition behavior. The morphology of the micelle and gel was investigated by atomic force microscopy (AFM). As a result, the micelles showed a core-corona spherical structure at concentration near CMC, while the gel showed a mountain-chain-like morphology picture. It was proposed that with increasing the micelle concentration the worm-like micelle clusters formed firstly and the gel was constructed by the packing of micelle clusters.     

The effect of shear on ordered block copolymer solutions

Block copolymers are extensively used in solution, especially aqueous solution, because of their amphiphilic character. This leads to the formation of lyotropic mesophases under given conditions of concentration and temperature. In many applications, block copolymer solutions are subjected to shear during processing (for example in drug delivery or when washing in detergent solutions) and thus it is of considerable interest to understand how shear affects the mesophase structure. Recent research has focussed on probing shear-induced structural transformations in lamellar, hexagonal and cubic-packed micellar phases using small-angle X-ray and neutron scattering.     

Controlling the properties of poly(amino ester urethane)–poly(ethylene glycol)–poly(amino ester urethane) triblock copolymer pH/temperature-sensitive hydrogel

A series of triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) was synthesized and characterized. Its aqueous solution can be used as a non-cytotoxic, biodegradable, and pH/temperature-sensitive hydrogel system. The copolymer solutions exhibited sol-to-gel and gel-to-sol transitions with increasing pH and temperature, respectively. The properties of this hydrogel system, such as its sol–gel transition diagram, mechanical properties, and degradation rate, can be controlled by modulating the PEG molecular weight, PAEU block length, copolymer concentration, or structure of the monomers. The presence of urethane groups and ionized tertiary amine groups in the copolymer solution at lightly acidic pH may lead to a strong interaction of the copolymer with formulated bioactive therapeutic agents, while the existence of the gel state under physiological conditions (37 °C, pH 7.4) may enable this copolymer hydrogel to be applicable as a drug/protein carrier.     

Spontaneous formation of gold nanoparticles in poly(ethylene oxide)-poly(propylene oxide) solutions: solvent quality and polymer structure effects

We report here on the effects that the solution properties of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers have on the reduction of hydrogen tetrachloroaurate(III) hydrate (HAuCl4.3H2O) and the size of gold nanoparticles produced. The amphiphilic block copolymer solution properties were modulated by varying the temperature and solvent quality (water, formamide, and their mixtures). We identified two main factors, (i) block copolymer conformation or structure (e.g., loops vs entanglements, nonassociated polymers vs micelles) and (ii) interactions between AuCl4- ions and block copolymers (attractive ion-dipole interactions vs repulsive interactions due to hydrophobicity), to be important for controlling the competition between the reactivities of AuCl4- reduction in the bulk solution to form gold seeds and on the surface of gold seeds (particles) and the particle size determination. The particle size increase observed with increased temperature in aqueous solutions is attributed to enhanced hydrophobicity of the block copolymer, which favors AuCl4- reduction on the surface of seeds. The lower reactivity and higher particle sizes observed in formamide solutions are attributed to the shielding of ion-dipole interaction between AuCl4- ions and block copolymers by formamide, which overcomes the beneficial effects of formamide on the block copolymer conformation (lower micelle concentration).     

Block copolymer-mediated synthesis of size-tunable gold nanospheres and nanoplates

We have successfully controlled the size and shape of isotropic and anisotropic gold nanocrystals through a one-step reaction by using amphiphilic polyethylene oxide-polystyrene oxide block copolymers as both reductant and stabilizing agents in water solution. Spherical or quasispherical nanoparticles were obtained at room temperature with tunable mean sizes and polydispersities depending on reaction conditions, that is, on copolymer block length, and copolymer and gold salt concentrations. By moderate increases of reaction temperature up to 65 degrees C, progressive formation of single-crystalline gold nanoplates in good yields takes place (up to 70%) without the necessity of additional reactants or growing solutions. These nanoplates are characterized by lateral mean sizes between 0.1-1.2 microm depending on copolymer concentration and reaction temperature, with mainly truncated or rounded triangular shapes with {111} planes as two basal surfaces. This allows us to tune the surface plasmon band of the nanoplates from ca. 850 nm to more than 1100 nm, well inside the near-infrared region (NIR), which enables the use of these type of nanostructures as a very promsing materials in applications such as optical coatings, SERS, and cancer cell hyperthermia. We proposed that the growth of these nanostructures can stem from a decrease in the reaction rate as temperature increases due to an enhanced copolymer hydrophobicity, which gives rise to a structure of interacting micelles formed from the fluid via a percolation transition (known as "soft gel") at elevated temperatures. In this way, reduction becomes slow enough to allow kinetic control of the reaction, and preferential adsorption of the copolymer molecules/micelles on certain crystallographic planes can favor the growth of certain nanocrystal facets to give the final structure. This alternative water-based system provides a more convenient and environmentally benign route to the synthesis of shape-controlled noble-metal nanocrystals in high yield because it does not involve toxic organic solvents or reagents and serves as a bridge between two frontline discipline: the block copolymeric science and anisotropic nanoparticles.     

Biodegradable and stimuli sensitive amphiphilic graft copolymers and their sol–gel phase transition behavior

pH and temperature‐sensitive biodegradable poly(β‐aminoester)‐graft‐poly(ε‐caprolactone)‐block‐methoxy poly(ethylene glycol) (PBAE‐g‐PCL‐b‐mPEG) amphiphilic graft copolymers with different molecular weights were synthesized. The structure of these copolymers was adjusted by varying the feed ratios of ε‐caprolactone to methoxy poly(ethylene glycol)s (mPEG), amine and diacrylate monomer amounts and the molecular weight of mPEG. Aqueous solutions of these copolymers formed micelles at lower concentrations; however, the concentrated solutions showed a reversible sol–gel transition property depending on both pH and temperature changes under representative physiological conditions (pH 7.4, 37°C). The effects of the molecular weight of pH‐sensitive poly(β‐aminoester) block and mPEG group, the hydrophobic to hydrophilic block ratio (PCL/mPEG) and the concentration of the copolymer on the sol–gel transition were investigated. Proton nuclear magnetic resonance (¹H NMR) and gel permeation chromatography measurements were used to characterize the structure of the synthesized copolymers. The self‐assemble behavior and critical micelle concentration of the amphiphilic copolymers were estimated in phosphate buffer solution using fluorescence spectroscopy. The gelling behavior was measured by using tube inversion method. At pH 7.4, all copolymer solutions prepared 20 wt% concentration indicated sol–gel transition with increasing temperature. In vitro degradation experiments displayed that the synthesized graft copolymers mostly degraded hydrolytically within 20 days under physiological conditions. In order to investigate the potential application of synthesized hydrogels in drug delivery, Methylene Blue was used and approximately 70% of the loaded amount was released in 120 hr. The findings indicate that obtained graft copolymers can be used as injectable biodegradable carriers for pharmaceutical drugs. Copyright © 2015 John Wiley & Sons, Ltd.     

温敏性PCL-PEG-PCL水凝胶的合成、表征及蛋白药物释放

考察了温敏性PCL-PEG-PCL水凝胶中聚乙二醇(PEG)及聚己内酯(PCL)不同嵌段组成对其溶胶-凝胶相转变温度以及亲水性药物(牛血清白蛋白, BSA)释放速率的影响. 采用开环聚合法, 以辛酸亚锡为催化剂、PEG1500/PEG1000为引发剂, 与己内酯单体发生开环共聚, 合成了一系列具有不同PEG和PCL嵌段长度的PCL-PEG-PCL型三嵌段共聚物. 通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行了表征. 共聚物的溶胶-凝胶相变温度由翻转试管法测定. 利用透射电镜、核磁共振氢谱及荧光探针技术证实了该材料在水溶液中胶束的形成. 以BSA为模型蛋白药物, 制备载药水凝胶, 利用microBCA法测定药物在释放介质中的浓度, 研究其体外释放行为. 实验结果表明, 共聚物的溶胶-凝胶相变温度与PCL及PEG嵌段长度紧密相关, 即在给定共聚物浓度情况下, 固定PEG嵌段长度而增加PCL嵌段长度, 会导致相变温度降低; 而固定PCL嵌段长度而增加PEG嵌段长度, 其相变温度相应升高. 水凝胶中蛋白药物的释放速率与疏水的PCL嵌段长度无关, 而与亲水的PEG嵌段长度密切相关, 即PEG嵌段越长, 蛋白药物释放越快.     

Switching the inside and the outside of aggregates of water-soluble block copolymers with double thermoresponsivity

Water-soluble block copolymers were prepared from the nonionic monomer N-isopropylacrylamide (NIPA) and the zwitterionic monomer 3-[N-(3-methacrylamidopropyl)-N,N-dimethyl]ammoniopropane sulfonate (SPP) by sequential free radical polymerization via the RAFT process. Such block copolymers with two hydrophilic blocks exhibit double thermoresponsive behavior in water: the poly-NIPA block shows a lower critical solution temperature, whereas the poly-SPP block exhibits an upper critical solution temperature. Appropriate design of the block lengths leads to block copolymers which stay in solution in the full temperature range between 0 and 100 degrees C. Both blocks of these polymers dissolve in water at intermediate temperatures, whereas at high temperatures, the poly-NIPA block forms colloidal hydrophobic associates that are kept in solution by the poly-SPP block, and at low temperatures, the poly-SPP block forms colloidal polar aggregates that are kept in solution by the poly-NIPA block. In this way, colloidal aggregates which switch reversibly can be prepared in water, and without any additive, their "inside" to the "outside", and vice versa. The aggregates provide microdomains and surfaces of different character, which can be controlled by a simple thermal stimulus.     

Rheology of aqueous solutions of polyglycidol-based analogues to pluronic block copolymers

The aqueous solution properties of a series of polyglycidol-poly(propylene oxide)-polyglycidol (PG-PPO-PG) block copolymers were investigated by means of rheology. The copolymers are considered as analogues to the commercially available Pluronic, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO), block copolymers in which the flanking PEO blocks are substituted by blocks of structurally similar PG bearing a hydroxyl group in each repeating monomer unit. In the dilute regime, the samples normally behave as Newtonian fluids. Shear thinning was observed only for the solutions of LGP65 (the copolymer of 50 wt % PG content) as well as at concentrations well above the critical micellization concentration for the rest of the copolymers. The zero shear viscosities exhibited pronounced maxima at PG content of 50 wt % and were found to decrease with increasing temperature. The concentrated solutions were investigated using oscillatory measurements. Large hystereses were observed during the temperature sweeps 15-70-15 degrees C. The evolutions of the loss and storage moduli with frequency, PG content, and temperature displayed transitions from a non-elastic to elastic behavior of the solutions. A phase diagram showing areas of predominant elasticity or fluidity was constructed.     

Thermosensitive behavior of poly(ethylene glycol)/poly(2‐(N,N‐dimethylamino)ethyl methacrylate) double hydrophilic block copolymers

The poly(ethylene glycol)/poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (PEG/PDMAEMA) double hydrophilic block copolymers were synthesized by atom transfer radical polymerization using mPEG‐Br or Br‐PEG‐Br as macroinitiators. The narrow molecular weight distribution of PEG/PDMAEMA block copolymers was identified by gel permeation chromatography results. The thermosensitivity of PEG/PDMAEMA block copolymers in aqueous solution was revealed to depend significantly on pH, ionic strength, chain structure, and concentration of the block copolymers. By optimizing these factors, the cloud point temperature of PEG/PDMAEMA block copolymers can be limited within body temperature range (30–37 °C), which suggests that PEG/PDMAEMA block copolymers could be a good candidate for drug delivery systems. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 503–508, 2010     

Injectable hydrogels as unique biomedical materials

A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.     

Robust control of microdomain orientation in thin films of block copolymers by zone casting

Block copolymers with chemically immiscible segments exhibit a variety of microphase-separated nanostructures on the scale of 10-100 nm. Controlling the orientation of these microphase separated nanostructures is vital in many applications such as lithography, membranes, data storage, and so forth. Typical strategies involve the use of external fields or patterned substrates. Here, we report a robust zone casting technique to achieve highly ordered thin films of block copolymers on centimeter-scale substrates. The robustness of this technique is its powerful control on diverse morphologies and exceptional tolerance on versatility of block copolymer chemistry as well as allowance of a wide spectrum of substrates. We demonstrate that perpendicular orientations with respect to the surface are achieved for block copolymers with both lamellar and cylindrical morphologies by controlling solution casting rate, temperatures, and block copolymer chemical structures. Thin films of both noncrystalline and crystalline block copolymers exhibit excellent orientational order and lateral order. However, the lateral order in the thin films of crystalline block copolymers shows dependence on casting temperature and melting temperature of the crystalline segment. Remarkably, all the ordering is independent of the substrates on which the block copolymer films are cast.     

Temperature-induced self-assembly of triple-responsive triblock copolymers in aqueous solutions

A series of triple-thermoresponsive triblock copolymers from poly(N-n-propylacrylamide) (PNPAM, A), poly(methoxydiethylene glycol acrylate) (PMDEGA, B), and poly(N-ethylacrylamide) (PNEAM, C) was synthesized by sequential reversible addition-fragmentation chain transfer polymerizations. Polymers of differing block sequences, ABC, BAC, and ACB, with increasing phase transition temperatures in the order A < B < C were prepared. Their aggregation behavior in dilute aqueous solution was investigated using dynamic light scattering, turbidimetry, and NMR spectroscopy. The self-organization of such polymers was found to dependent strongly on the block sequence. While polymers with a terminal low-LCST (lower critical solution temperature) block undergo aggregation above the first phase transition temperature at 20-25 °C, triblock copolymers with the low-LCST block in the middle show aggregation only above the second phase transition. The collapse of the middle block is not sufficient to induce aggregation but produces instead stable, unimolecular micelles with a collapsed middle block, as supported by NMR and fluorescence probe data. Continued heating of all copolymers led to two additional thermal transitions at 40-55 and 70-80 °C, which could be correlated to the phase transitions of the B and C blocks, respectively. All polymers show a high tendency for cluster formation, once aggregation is induced. The carrier abilities of the triple responsive triblock copolymers for hydrophobic agents were probed with the solvatochromic fluorescence dye Nile Red. With passing through the first thermal transition, the block copolymers are capable of solubilizing Nile Red. In the case of block copolymers with sequences ABC or ACB, which bear the low-LCST block at one terminus, notable amounts of dye are solubilized already at this stage. In contrast, the hydrophobic probe is much less efficiently incorporated by the BAC triblock copolymer, which forms unimolecular micelles. Only after the collapse of the B block, when reaching the second phase transition at about 45 °C, does aggregation occur and solubilization becomes efficient. In the case of ABC and ACB polymers, the hydrophobic probe seems to partition between the originally collapsed A chains and the additional hydrophobic chains formed after the collapse of the less hydrophobic B block.     

Adsorption of poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers at the silica-water interface

The adsorption of amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) and poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) copolymers in aqueous solution on silica and glass surfaces has been investigated by flow microcalorimetry, small-angle neutron scattering (SANS), surface forces, and complementary techniques. The studied copolymers consist of a poly(ethylene oxide) (PEO) block of M(n) = 5000 and a hydrophobic polyester block of poly(epsilon-caprolactone) (PCL) or poly(gamma-methyl-epsilon-caprolactone) (PMCL) of M(n) in the 950-2200 range. Compared to homoPEO, the adsorption of the copolymers is significantly increased by the connection of PEO to an aliphatic polyester block. According to calorimetric experiments, the copolymers interact with the surface mainly through the hydrophilic block. At low surface coverage, the PEO block interacts with the surface such that both PEO and PCL chains are exposed to the aqueous solution. At high surface coverage, a dense copolymer layer is observed with the PEO blocks oriented toward the solution. The structure of the copolymer layer has been analyzed by neutron scattering using the contrast matching technique and by tapping mode atomic force microscopy. The experimental observations agree with the coadsorption of micelles and free copolymer chains at the interface.     

Self-assembled structures of block copolymers in selective solvents reproduced by lattice Monte Carlo simulation

A lattice Monte Carlo (MC) simulation was applied to the study of block copolymers in selective solvent or amphiphilic surfactant solution on the segment level, hydrodynamic interactions being neglected. The code was found to be very efficient, employing a partial reptation mode as the elementary movement of the self-avoiding lattice chains. Typical self-assembled structures of block copolymers such as micelle, lamellae, hexagonal cylinder and bicontinuous networks have been successfully reproduced without any priori specification of structure. Order–disorder and order–order transitions of diblock copolymers are systematically studied by adjusting the temperature, the concentration or the block length ratio in a series computer simulations. The structural differences between micelles composed of ABA and BAB triblock copolymers are also explicitly revealed by direct visualisation of the underlying chain configurations. The simulation results are consistent with the experimental observations in the literature. This simulation approach is thus a very useful tool in the extensive investigation of self-assembled structures. It has the advantage that both micro-domains and chain configurations can be studied with only a comparatively modest call on computational resources.     

Pressure-induced reentrant micellization of amphiphilic block copolymers in dilute aqueous solutions

The pressure-induced structural changes of a block copolymer, poly(2-ethoxyethoxyethyl vinyl ether)-block-poly(2-hydroxyethyl vinyl ether) (pEOEOVE-b-pHOVE) in aqueous solutions, were studied by means of small-angle neutron scattering (SANS) and dynamic light scattering (DLS) from atmospheric pressure up to 400 MPa. pEOEOVE-b-pHOVE formed a spherical micellar structure above 40 degrees C due to poor solubility of pEOEOVE. Micellization phase diagram was determined by DLS, and a covex-upward pressure-temperature (P-T) phase diagram was obtained having a peak around (P,T)=(150 MPa,48 degrees C). The SANS curves at 50 degrees C were analyzed as a function of P. The micellar core size decreased by pressurizing at low P's (P相似文献   

THE VISCOELASTIC EFFECT ON THE FORMATION OF MESO-GLOBULAR PHASE OF DILUTE HETEROPOLYMER SOLUTIONS

Linear homopolymer chains in poor solvent exist either as individual crumpled single chain globules or asmacroscopic precipitate, depending on whether the solution is in the one- or the two-phase region. However, linearheteropolymer chains in dilute solution might be able to form stable mesoglobules made up of a limited number of chains ifthe degree of amphiphilicity of the chain is sufficiently high and the experimental conditions are appropriate. The self-assembly of block copolymers in a selective solvent is typical of such examples. In practice, the formation of stablemesoglobules can be directly related to the formation of novel polymeric nanopaticles in solution. In this article, we willaddress the formaton of mesoglobular phase not only on the basis of thermodynamics, but also from a kinetic point of view,which leads to the discussion of how viscoelasticity can affect the phase behavior of heteropolymer chains in dilute solution.The formation and stabilization of several different kinds of novel polymeric nanopedicles will be used to illustrate ourdiscussion.