Poly(N-isopropylacrylamide)-block-poly(acrylic acid) hydrogels: synthesis and rapid thermoresponsive properties

In this contribution, we reported the synthesis of poly(N-isopropylacrylamide)-block-poly(acrylic acid) (PNIPAAm-b-PAA) copolymer networks via sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. The PNIPAAm-b-PAA block copolymer networks were characterized by means of Fourier transform infrared spectroscopy (FTIR) and small angle X-ray scattering (SAXS). The volume phase transition (VPT) temperatures of the PNIPAAm-b-PAA hydrogels were measured by means of micro-differential scanning calorimetry (micro-DSC). It was found that the block copolymer hydrogels displayed the VPT temperatures lower than the control PNIPAAm hydrogel. Compared to the control PNIPAAm hydrogel, the deswelling and reswelling properties of the block copolymer hydrogels were significantly improved. The improved thermoresponsive properties of the PNIPAAm-b-PAA hydrogels have been interpreted on the basis of the formation of the architecture of the block copolymer networks.     

Poly(2-(dimethylamino)ethyl methacrylate)-b-poly(hydroxypropyl methacrylate) copolymers/bovine serum albumin complexes in aqueous solutions

Complexation ability of poly(2-(dimethylamino)ethyl methacrylate)-b-poly(hydroxy propyl methacrylate) (PDMAEMA-b-PHPMA) amphiphilic doubly thermo-responsive block copolymers, and their quaternized counterparts QPDMAEMA-b-PHPMA, toward bovine serum albumin (BSA) is studied in aqueous solutions. The PDMAEMA-b-PHPMA amphiphilic block copolymers self-assemble in nanostructured aggregates with PDMAEMA coronas having different inner structure and micro-polarity depending on the solubilization protocol utilized when inserted in aqueous media. By incorporating different BSA concentrations, we investigate the copolymer–protein interactions by light scattering measurements in aqueous solutions in a broad temperature range, utilizing different solubilization protocols for the copolymers. Fluorescence spectroscopy and ζ-potential measurements were also utilized to investigate the structure and properties of the copolymer/protein complexes formed in each case. Such knowledge may lead to a better understanding of the inner structure and micro polarity of the nanostructured aggregates formed by the novel (Q)PDMAEMA-b-PHPMA copolymers, along with their potential abilities in nanocarrier formation, protein complexation, stabilization, and delivery.     

开管毛细管电色谱分析3种解热镇痛药物

针对生物体液样品开展药物的绿色高效毛细管电泳分离分析具有重要的研究意义。该研究以3种解热镇痛药（4-氨基安替比林、氨基比林及非那西汀）为研究对象,以嵌段聚合物为涂层,建立了药物的开管毛细管电色谱（OT-CEC）分析新策略。首先,采用活性/可控自由基可逆加成-断裂链转移聚合方法,合成制备得到了两亲性嵌段聚合物-聚（苯乙烯-甲基丙烯酸缩水甘油酯）（P（St-GMA））,并将其涂覆到毛细管内壁;其次,通过考察影响OT-CEC分离效率的关键因素,包括嵌段聚合物的聚合时间、涂覆毛细管嵌段聚合物的浓度、电泳运行缓冲液的种类和pH值、有机溶剂添加剂等,优化了3种解热镇痛药物的OT-CEC分离条件;最终发现,不需添加任何有机溶剂及表面活性剂,仅采用50.0 mmol/L乙酸钠-乙酸（pH 5.7）作为OT-CEC的缓冲溶液,就能实现3种解热镇痛药物的基线分离。在8.0~2.5×10³ μmol/L范围内,分析物峰面积与其对应的浓度呈现良好的线性关系,相关系数（R²）均大于0.995,检出限为1.0~2.5 μmol/L。结果表明：P（St-GMA）在溶液中自组装所形成的类表面活性剂胶团结构增强了两亲性嵌段聚合物与解热镇痛药物之间的相互作用,显著提升了解热镇痛药物的OT-CEC分离效率。该工作不仅为制备新型聚合物及调控嵌段聚合物的自组装行为提供了研究思路,也展示了两亲性嵌段聚合物在药物的绿色OT-CEC分析中的实际应用潜力。     

Poly(2-[dimethylamino]ethyl methacrylate)-b-poly(hydroxypropyl methacrylate)/DNA polyplexes in aqueous solutions

This study involves the investigation of the complexation ability of poly(2-[dimethylamino]ethyl methacrylate)-b-poly(hydroxypropyl methacrylate) (PDMAEMA-b-PHPMA) amphiphilic pH and thermoresponsive block copolymers, and their quaternized counterparts QPDMAEMA-b-PHPMA, toward short DNA in aqueous solutions. The PDMAEMA-b-PHPMA amphiphilic block copolymers present various self-assembly characteristics when inserted into aqueous media, depending on the composition, the solubilization protocol, the acidity and the temperature of the aqueous media. Copolymer aggregates-DNA interactions and nanostructure formation after complexation are investigated by dynamic light scattering and intensity measurements in aqueous solutions in a fixed temperature range, utilizing two different solubilization protocols for the copolymers. Ethidium bromide assays by fluorescence spectroscopy and ζ-potential measurements were also utilized to investigate the structure and properties of the DNA/copolymer polyplexes. The interpretation of such physicochemical characterization provides extra comprehension of the novel (Q)PDMAEMA-b-PHPMA copolymers self-assembly characteristics and assesses their ability for DNA complexation, stabilization, and delivery.     

Studies on the self-assembly behavior of the amphiphilic block copolymer of PSt-b-PAA in apolar solvents with polar fluorescent probe

The block copolymer of polystyrene-b-poly(butyl acrylate) (PSt-b-PBA) with a well-defined structure was synthesized by atom transfer radical polymerization (ATRP); its structure was characterized, and the living polymerization was also validated by gel permeation chromatography, Fourier transform infrared, and ¹H NMR measurements. Then, the amphiphilic block copolymer of polystyrene-b-poly(acrylic acid) (PSt-b-PAA) has been prepared by hydrolysis of PSt-b-PBA, and copolymers of PSt-b-PAA with longer PSt blocks and shorter PAA blocks were obtained by controlling the conditions of ATRP polymerization. The reversed micelle solution of PSt-b-PAA in toluene was prepared by using the single-solvent dissolving method, and the reverse micellization behavior of PSt-b-PAA in toluene was mainly investigated in this paper. The fluorescent probe technique was used by using polar fluorescence compound N-(1-Naphthyl)ethylenediamine dihydrochloride (NEAH) as a polar fluorescent probe to study the reverse micellization behavior of PSt-b-PAA. It was found that the reverse micellization behaviors of PSt-b-PAA in toluene can be clearly revealed by using NEAH as a polar fluorescence probe, and the critical micelle concentrations (cmcs) can be well displayed. The experimental results showed that the self-assembling behavior of PSt-b-PAA in toluene depends apparently on the microstructure of the macromolecules and is also influenced by the temperature. For the copolymers of PSt-b-PAA with the same length of hydrophobic PSt blocks, the copolymer with a longer hydrophilic block PAA has lower cmc, and at higher temperature, the copolymer has lower cmc.     

Synthesis of poly(N,N‐dimethylacrylamide)‐block‐poly(ethylene oxide)‐block‐poly(N,N‐dimethylacrylamide) and its application for separation of proteins by capillary zone electrophoresis

A series of well‐defined triblock copolymers, poly(N, N‐dimethylacrylamide)‐block‐poly(ethylene oxide)‐block‐poly(N, N‐dimethylacrylamide) (PDMA‐b‐PEO‐b‐PDMA) synthesized by atom transfer radical polymerization, were used as physical coatings for protein separation. A comparative study of EOF showed that the triblock copolymer presented good capillary coating ability and EOF efficient suppression. The effects of the M_r of PDMA block in PDMA‐b‐PEO‐b‐PDMA triblock copolymer and buffer pH on the separation of basic protein for CE were investigated. Moreover, the influence of the copolymer structure on separation of basic protein was studied by comparing the performance of PDMA‐b‐PEO‐b‐PDMA triblock copolymer with PEO‐b‐PDMA diblock copolymer. Furthermore, the triblock copolymer coating showed higher separation efficiency and better migration time repeatability than fused‐silica capillary when used in protein mixture separation and milk powder samples separation, respectively. The results demonstrated that the triblock copolymer coatings would have a wide application in the field of protein separation.     

A novel amphipathic block copolymer coating forming micelle-like aggregates for separation of steroids in open tubular capillary electrochromatography

A new amphipathic block copolymer, poly(tert-butyl acrylate)₁₂₇-block-poly(glycidyl methacrylate)₈₆, was developed for the coating in open tubular capillary electrochromatography. The self-assembly characters of the coating, which could form micelle-like aggregates under proper conditions, were observed by atomic force microscopy. Compared with bare capillary, this coating could act as surfactant and lead to improve the separation of steroids. In addition, the influence of pH, buffer concentration and organic solvents on the separation was investigated. The best separation of the three model steroid analytes could be achieved using 20.0 mM borate buffer at pH 10.5. For covalent bonding, the coating showed good repeatability and stability with RSD of u_EOF less than 3.3%. Then, this proposed method was well validated with good linearity (≥0.999), recovery (91.0-94.0%) and repeatability, and was successfully used for separation of steroids in spiked serum samples, which indicated that this new OT-CEC method could provide a potential tool to determine steroids in real biological system without interference.     

Growth of two-layer copolymer as the stationary phase with very high separation efficiency for separating peptides in capillary electrochromatography

Open tubular CEC (OT-CEC) column with a very high separation efficiency was prepared for peptides separation. A pretreated silica-fused capillary was reacted with 3-(methacryloxy) propyltrimethoxysilane followed by vinylbenzyl chloride and divinylbenzene to produce first thin monolithic monolayer. The second copolymer layer was formed on thin monolithic monolayer of the capillary by reversible addition-fragmentation transfer polymerization of N-phenylacrylamide and styrene. The key parameters including buffer pH value and organic modifier were systematically evaluated to provide the optimal chromatographic condition. The resultant OT-CEC columns were validated by separating a synthetic mixture of peptides and cytochrome C tryptic digest in capillary electrochromatography. The number of theoretical plates as high as 2.4 million per column was achieved for synthetic mixture peptides. In addition, the fabricated OT-CEC column also resolved more than 18 high-efficiency digestion peptides from a mixture containing tryptic digest of cytochrome C. The column to column and inter- to intraday repeatabilities of OT-CEC column through RSD% were found better than 3.0%, exhibiting satisfactory stability and repeatability of the two-layer deposited OT-CEC column. The results reveal that the open tubular capillary column modified with two-layer copolymer shows the great prospect for the separation of proteins in capillary electrochromatography.     

Open tubular capillary electrochromatography with block co-polymer coating for separation of β-lactam antibiotics

Unique block co-polymer P(MAn-St-NIPAm) has been successfully synthesized by reversible addition fragmentation chain transfer radical polymerization protocol. Based on the tunable hydrophobic/hydrophilic properties of the block co-polymer, a new open tubular capillary electrochromatography (OT-CEC) system has been constructed with the prepared block co-polymer as the coating and applied in analysis of β-lactam antibiotics in serum samples.     

Self-assembly of poly(ethylene glycol)-block-polypyridine copolymer into micelles and at silica surface: effect of molecular architecture on silica dispersion

We have newly synthesized amphiphilic block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic pyridine segments (PEG-b-Py). Chain transfer agent-terminated PEG was subsequently chain-extended with 3-(4-pyridyl)-propyl acrylate to obtain PEG-b-Py by reversible additional-fragmentation chain transfer polymerization. Particularly, the effect of varying molecular weight (Mn) of PEG (Mn?=?2,000 and 5,000) and Py in the block copolymers was investigated in terms of critical micelle concentration, pyrene solubilization, micelle size distribution, and association number per micelle. Based on the amphiphilic balance, PEG-b-Pys formed core-shell type polymer micelle. The association number of PEG2k-b-Py was higher than that of PEG5k-b-Py, suggesting the degree of phase separation strongly depended on PEG Mn. Furthermore, the adsorption of PEG-b-Py copolymer onto silica nanoparticles as dispersant was studied to estimate the effect of PEG Mn in the copolymers and their solubility in the medium on the adsorption. Adsorbed density of PEG2k-b-Py copolymer onto silica nanoparticle was higher than that of PEG5k-b-Py, which was significantly correlated with the degree of phase separation. Furthermore, the adsorbed amount of copolymer increased with the increase in ionic strength due to the reduced solubility of PEG in the buffer solution. The resultant dispersion stability was highly correlated with the graft density of copolymer onto silica surface. However, the stability of PEG2k-b-Py coated particles was lower than that with PEG5k-b-Py, this is attributed to the relatively thin layer of PEG at the silica surface, which cannot provide the system with sufficient steric stabilization as the salt concentration increases. These fundamental investigations for the surface modification of the nanoparticle provide the insight into the highly stable colloidal dispersion, particularly in the physiological condition with high ionic strength.     

Electric-field-assisted assembly and alignment of polystyrene-b-poly(acrylic acid) micelles

In this paper, we describe an efficiently physical method of electric-field-assisted assembly and alignment of block copolymer micelles. Amphiphilic block copolymer polystyrene-b-poly(acrylic acid) (PS-b-PAA) self-assembles into spherical micelles in water consisting of a core formed by the insoluble PS blocks and a shell formed by the soluble PAA blocks. When applying an alternating voltage to micelles solution dispersed onto a thin gap of coplanar metallic electrode, we generate directional arrays of highly ordered aggregates in long range. The formation of the ordered aggregates is due to the adjustment of interactions between micelles induced by dielectrophoretic forces in alternating electric field. The morphologies and arrays of particles become more regular with increasing of the strength and frequency of electric field. Voltage and frequency of the electric field and other parameters, such as particles concentration and, the viscosity and dielectric constant of the medium, affect the assembly process.     

Synthesis and pH-sensitive micellization of doubly hydrophilic poly(acrylic acid)-b-poly(ethylene oxide)-b-poly(acrylic acid) triblock copolymer in aqueous solutions

A doubly hydrophilic triblock copolymer poly(acrylic acid)-b-poly(ethylene glycol)-b-poly(acrylic acid) (PAA-b-PEO-b-PAA) with M _w/M _n = 1.15 was synthesized by atom transfer radical polymerization of t-butyl acrylate (tBA), followed by acidolysis of the PtBA blocks. The pH-sensitive micellization of PAA-b-PEO-b-PAA in acidic solution was investigated by potentiometric titration, fluorescence spectrum, dynamic light scattering and zeta potential. The pK _a was 6.6 and 6.0 in deionized water and in 0.1 mol/L NaCl solution, respectively. The copolymer formed micelles composed of a weakly hydrophobic core of complexed PAA and PEO and a hydrophilic PEO shell in 1 mg/mL solution at pH < 5.5 due to hydrogen bonding. The critical micelle concentration was 0.168 mg/mL at pH 2.0. At pH < 4.5, steady and narrow distributed micelles were formed. Increasing pH to 5.0, unsteady and broad distributed micelles were observed. At pH > 5.5, the micelle was destroyed owing to the ionization of the PAA blocks.     

Hydroxyethylcellulose-graft-poly(2-(dimethylamino)ethyl methacrylate) as physically adsorbed coating for protein separation by CE

In this work, a novel graft copolymer, hydroxyethylcellulose-graft-poly(2-(dimethylamino)ethyl methacrylate) (HEC-g-PDMAEMA), used as physical coatings of the bare fused-silica capillaries, was synthesized by using ceric ammonium nitrate initiator in aqueous nitric acid solution. EOF measurement results showed that the synthesized HEC-g-PDMAEMA graft copolymer-coated capillary in this paper could suppress EOF effectively compared to the bare fused-silica capillary, and efficient separations of basic proteins were also achieved. The electrical charge of the coated capillary wall could be modulated by varying not only the pH of the running buffer, but also the grafting ratio of poly(2-(dimethylamino)ethyl methacrylate) grafts, which makes possible the analysis of basic and acidic proteins in the same capillary. The effects of poly(2-(dimethylamino)ethyl methacrylate) grafting ratio in HEC-g-PDMAEMA and buffer pH on the separation of basic proteins for capillary electrophoresis were investigated in detail. Furthermore, egg white proteins and milk powder samples were separated by the HEC-g-PDMAEMA-coated capillary. The results demonstrated that the HEC-g-PDMAEMA copolymer coatings have great potential in the field of diagnosis and proteomics.     

Miniemulsion cross-linking: A convenient route to hollow polymeric nanocapsule with a liquid core

Miniemulsion stabilized by poly(2-(dimethylamino) ethyl methacrylate)-block-poly(butyl methylacrylate) (PDMAEMA-b-PBMA) diblock copolymers has been used as liquid templates for the synthesis of polymer nanocapsules via quaternization cross-linking of PDMAEMA segments of the copolymer by 1,2-bis(2-iodoethoxy)ethane (BIEE) crosslinkers. PDMAEMA-b-PBMAs here as a stabilizer in miniemulsion with different molecular weights led to a size variation in diameters of nanocapsules, demonstrating the capsules have potential design capability of this technique. The solution behavior of the capsules has been also investigated in this paper.     

Preparation of Biomimetic Zwitterionic Core Cross-Linked Nanocarriers for Control Release of Bioactive Agents

Biomimetic core cross-linked nanocarriers (CCL-NCs) with zwitterionic shell was constructed from an amphiphilic block copolymer poly(2-(dimethylamino) ethyl methacrylate-co-carboxybetaine)-b-polystyrene ((PDMAEMA-co-PCB)-b-PS) via mini-emulsion RAFT polymerization. CCL-NCs present in this report possess properties of redox-sensitivity, limited unspecific protein adsorptions and low cytotoxicity, which highly enhance their potential application in drug delivery. Morphology of CCL-NCs was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. The control release process has also been investigated under three different conditions with or without dithiothreitol (DTT) at pH 5.4, 6.5 and 7.4.     

Hierarchical porous nanofibers of carbon@nickel oxide nanoparticles derived from polymer/block copolymer system

The triblock copolymer (PAA-b-PAN-b-PAA) is prepared by reversible addition-fragmentation chain-transfer polymerization, and then blended with polymer (PAN) and metal hydroxide (Ni(OH)₂) as a precursor for heat-treatment. A composite material of hierarchical porous nanofibers and nickel oxide nanoparticles (HPCF@NiO) is prepared by electrospinning combined with high-temperature carbonization. The effects of the ratio of PAA and PAA-b-PAN-b-PAA on the internal structure of nanofibers and their electrochemical properties as positive electrode materials are investigated. The experimental results show that when the ratio of PAA to PAA-b-PAN-b-PAA is 1.3 to 0.4, it has good pore structure and excellent electrochemical performance. At the current density of 1 A/g, the specific capacitance is 188.7 F/g and the potential window is −1 V to 0.37 V. The asymmetric supercapacitor assembled with activated carbon as the negative electrode materials has a specific capacitance of 21.2 F/g in 2 mol/L KOH and a capacitance retention of 85.7% after 12,500 cycles at different current density.     

Self‐assembly of thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) micelles for drug delivery

Self‐assembled thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) (PAA‐b‐PNIPAM) micelles for entrapment and release of doxorubicin (DOX) was described. Block copolymer PAA‐b‐PNIPAM associated into core‐shell micelles in aqueous solution with collapsed PNIPAM block or protonated PAA block as the core on changing temperature or pH. Complexation of DOX with PAA‐b‐PNIPAM triggered by the electrostatic interaction and release of DOX from the complexes due to the changing of pH or temperature were studied. Complex micelles incorporated with DOX exhibited pH‐responsive and thermoresponsive drug release profile. The release of DOX from micelles was suppressed at pH 7.2 and accelerated at pH 4.0 due to the protonation of carboxyl groups. Furthermore, the cumulative release of DOX from complex micelles was enhanced around LCST ascribed to the structure deformation of the micelles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5028–5035, 2008     

Electrostatic force microscopy measurements of CdSe-PS nanoparticles and CdSe-PS/poly(styrene-b-butadiene-b-styrene) nanocomposites

Electrostatic force microscopy (EFM) measurements were performed to analyze the conductive properties of CdSe nanoparticles functionalized with polystyrene (PS) brushes and embedded in a poly(styrene-b-butadiene-b-styrene) triblock copolymer. CdSe nanoparticles were synthesized aqueously and functionalized with polystyrene chains by the grafting through technique. CdSe-PS nanoparticles obtained after 5 and 8 h of polymerization were analyzed, in order to study the effect of the molecular weight of PS chains on conductive properties. EFM results showed the maintenance of the conductive properties of CdSe nanoparticles through functionalization reactions and even when they were confined in the block copolymer. Due to the low differences between the values obtained in the response of the samples to the charged tip, no effect of the molecular weight of brushes was confirmed.     

Ring-opening polymerization of l-lactide in supercritical carbon dioxide using PDMS based stabilizers

Ring-opening suspension polymerization of l-lactide in supercritical CO₂ (scCO₂) was investigated in the presence of different stabilizer architectures based on poly(dimethyl siloxanes) (PDMS). Two amphiphilic AB type block copolymers, a graft copolymer, and an ester-capped PDMS were selected to find their efficacy as stabilizers for the synthesis of poly(l-lactide) (PLLA) in scCO₂. The stabilizer’s efficiency was analyzed in terms of the molecular weight, yield, and particle morphology of PLLA. The block copolymers, poly(dimethylsiloxane)-b-poly(acrylic acid) (PDMS-b-PAA) and poly(dimethylsiloxane)-b-poly(methacrylic acid) (PDMS-b-PMA) were found to be effective, leading to the formation of fine, discrete PLLA microparticles. On the other hand, the graft copolymer, poly(dimethylsiloxane-g-pyrrolidonecarboxylic acid) (PDMS-g-PCA) and acetylated PDMS (PDMS-OAc) failed to give an enough stabilization to the PLLA due to their short polymer-philic chains, resulting in hard agglomerates.     

Determination of Phosphoamino Acids by 6-Oxy-(N-succinimidyl acetate)-9-(2′-methoxycarbonyl)fluorescein and MEKC with LIF Detection

The fluorescent reagent 6-oxy-(N-succinimidyl acetate)-9-(2′-methoxycarbonyl)fluorescein (SAMF), has been newly synthesized for use as a label for characterization of phosphoamino acids by micellar electrokinetic capillary electrophoresis (MEKC) with laser-induced fluorescence (LIF) detection. The conditions for derivatization and separation of the phosphoamino acids, including pH, concentration of electrolyte, and Brij-35 concentration were optimized in detail. Derivatization was performed at 35 °C for 10min in borate buffer (pH 8.0). The derivatives were separated to baseline by use of running buffer containing 50 mM borate and 20 mM Brij-35 at pH 9.3. Detection limits ranged from 5 × 10^?11 to 1 × 10^?9 mol L^?1 (signal to noise ratio = 3). The method was used for characterization of the phosphoamino acids in a sample from hydrolysis of a novel protein kinase from tobacco cells.