阳离子型温敏水凝胶的合成与性质

阳离子型温敏水凝胶的合成与性质王昌华卢英先曹维孝（北京大学化学与分子工程学院北京１００８７１）关键词热缩温敏水凝胶，Ｎ 异丙基丙烯酰胺，Ｎ 乙烯基吡啶氟硼酸盐，Ｎ 甲基 ４ 乙烯基吡啶硫酸甲酯盐水凝胶可看作是水溶或亲水高分子的一种亲水网络．多数...     

Synthesis of hydrophilic microspheres with LCST close to body temperature for controlled dual‐sensitive drug release

Novel stimuli‐responsive hydrophilic microspheres were prepared by free radical polymerization of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MA), as hydrophilic monomers, and N‐isopropylacrylamide (NIPAAm) and N,N′‐ethylenebisacrylamide (EBA), as thermo‐sensitive monomer and crosslinker, respectively. Hydrophilic comonomers were introduced in the macromolecular network to synthesize materials with tunable thermal behavior. In addition, by introducing in the polymerization feed both a hydrophilic and a pH‐sensitive monomer, such as MA, dual stimuli‐responsive (pH and temperature) hydrogels were synthesized. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and the shape of hydrogels was found to strictly depend on the concentration of monomers in the polymerization feed. Thermal analyses showed negative thermo‐responsive behavior with pronounced water affinity of microspheres at a temperature lower than lower critical solution temperature (LCST). In our experiment, the LCST values of the hydrogels were in the range 34.6–37.5°C, close to the body temperature, and the amount of hydrophilic moieties in the polymeric network allows to collect shrinking/swelling transition temperatures higher than the LCST of NIPAAm homopolymers. In order to test the preformed materials as drug carriers, diclofenac diethylammonium salt (DDA) was chosen and drug entrapment percent was determined. Drug release profiles, in media at different temperature and pH, depend on hydrogels crosslinking degree and drug–bead interactions. By using semi‐empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and thermal properties of a novel lactose‐containing poly(N‐isopropylacrylamide‐co‐acrylamidolactamine) hydrogel

An improved, simple, and efficient method for the synthesis of lactose‐containing monomer acrylamidolactamine (LAM) has been reported. Free radical copolymerization of this monomer with N‐isopropylacrylamide (NIPAM) in the presence of the crosslinking reagent N,N′‐methylenebisacrylamide (BisA) (1.2 mol %) proceeded smoothly in an aqueous solution using potassium persulfate (KPS) and N,N,N′,N′‐tetramethylethylenediamine (TMEDA) as the initiating system and gave transparent hydrogels. Reactivity ratios were estimated from copolymerization reactions carried out in solution without BisA crosslinker and at low conversion, by using both linearization and nonlinearization methods. They were found to be r_LAM = 0.75 and r_NIPAM = 1.22. The swelling behavior of the hydrogels was studied by immersion of the hydrogels in deionized water at different temperatures. Equilibrium water uptake was increased when the LAM content was higher than 47 mol %, and reached ≈ 44‐fold with 100 mol % LAM at room temperature. Depending on the composition, the gels showed sharp swelling transitions with small changes in temperature. Differential scanning calorimetry (DSC) was used to characterize the swelling transition and the organization of water in the copolymer hydrogels. The amounts of freezable water in these hydrogels ranged from 81 to 89%, and was not correlated to the content of the sugar monomer. These gels have potential applications as biocompatible materials. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1393–1402, 1999     

Temperature‐responsive linear polyelectrolytes and hydrogels based on [2‐(methacryloyloxy)ethyl] trimethylammonium chloride and N‐isopropylacrylamide and their complex formation with potassium hexacyanoferrates (II,III)

Water‐soluble temperature‐responsive polyelectrolytes and hydrogels have been synthesized by γ‐radiation copolymerization of [2‐(methacryloyloxy)‐ethyl]trimethylammonium chloride with N‐isopropylacrylamide. Complex formation of soluble copolymers with potassium hexacyanoferrates (II, III) was studied in aqueous solutions. It was shown that, depending on the concentration and temperature, the formation of soluble or insoluble polycomplexes is observed. The hydrogels show good ability to absorb potassium hexacyanoferrates (II, III) from aqueous solutions. Sorption ability of hydrogels depends on the content of cationic monomer in copolymer and the nature of coordination ion. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 515–522, 2004     

Studies on Curcumin Loaded Poly(N-isopropylacrylamide) Silver Nanocomposite Hydrogels for Antibacterial and Drug Releasing Applications

Design of silver nanoparticles containing poly(N-isopropylarclamide) (PNIPAAm) hydrogels were prepared by free-radical polymerization of N-isopropylarclamide as an environmentally sensitive monomer and MBA as a crosslinker in an aqueous medium. The embedded silver nanocomposite hydrogels (AgNCH) structure were characterized by, UV-Vis, FTIR, DLS, TEM and X-ray analysis. Curcumin loading and release characteristics were performed for PNIPAAm hydrogel, silver ions loaded hydrogels as well as silver nanocomposite hydrogels. These curcumin loaded silver nanocomposite hydrogels exhibit excellent antibacterial action on Escherichia coli (E. coli). Therefore, the present study clearly provides novel antimicrobial hydrogels which are potentially useful in biomedical applications.     

Fabrication of novel temperature and pH sensitive poly (N-isopropylmaleamic acid-co-acrylonitrile) hydrogels

To combine temperature and pH sensitive capabilities, N-isopropylmaleamic acid (NIPMMA), having isopropylamide group and weakly acidic group (–COOH), was synthesized and used as a precursor for fabrication of temperature and pH sensitive hydrogels. In this paper, a new class of intelligent hydrogel with pH and temperature sensitivity originated from only one precursor (NIPMMA) was designed and demonstrated. Resultant poly(NIPMMA-co-acrylonitrile) [P(NIPMMA-co-AN)] hydrogels were characterized by Fourier transform infrared spectroscopy for structural determination and scanning electron microscope for morphology observation. Their temperature and pH sensitive behaviors were also examined in detail. The data obtained exhibited that the magnitude of sensitive properties of P(NIPMMA-co-AN) hydrogels depended on the composition ratio of two precursors. By increasing the content of NIPMMA, the temperature and pH sensitive capabilities of P(NIPMMA-co-AN) hydrogels were improved correspondingly since AN has no sensitivity upon temperature or pH changes.     

Synthesis and characterization of thermoresponsive hydrogels cross-linked with acryloyloxyethylaminopolysuccinimide

Biodegradable cross-linkers acryloyloxyethylaminopolysuccinimide (AEA-PSI) were obtained by microwave irradiation using maleic anhydride as materials. With AEA-PSI cross-linker, cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content, thermodynamics stability, and enzymatic degradation properties were investigated. By alternating the NIPAAm/AAc molar ratio, hydrogels were synthesized to have LCST in the vicinity of 37 °C. The LCST of AEA-PSI-cross-linked P(NIPAAm-co-AAc) hydrogels was significantly influenced by monomer ratio of the NIPAAm/AAc but not by the cross-linking density within the polymer network. The water content of AEA-PSI-cross-linked P(NIPAAm-co-AAc) hydrogels was more than 90% even at 37 °C, which was controlled by the monomer molar ratio of NIPAAm/AAc, swelling media, and the cross-linking density. The thermodynamics stability was also characterized by thermogravimetry. In enzymatic degradation studies, breakdown of the AEA-PSI-cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on the cross-linking density. Submitted to Colloid and Polymer Science, 2007-1-28.     

Biodegradable thermo‐ and pH‐responsive hydrogels for oral drug delivery

In this article, novel smart hydrogels based on biodegradable pH sensitive poly(L ‐glutamic acid‐g‐2‐hydroxylethyl methacrylate) (PGH) chains and temperature‐sensitive hydroxypropylcellulose‐g‐acrylic acid (HPC‐g‐AA) segments were designed and synthesized. The influence of pH and temperature on the equilibrium swelling ratios of the hydrogels was discussed. The optical transmittance of the hydrogels was also changed as a function of temperature, which reflecting that the HPC‐g‐AA part of the hydrogels became hydrophobic at the temperature above the lower critical solution temperature (LCST). At the same time, the LCST of the hydrogels had a visible pH‐dependent behavior. Scanning electron microscopic analysis revealed the morphology of the hydrogels before and after enzymatic degradation. The biodegradation rate of the hydrogels was directly related to the PGH content and the pH value. The in vitro release of bovine serum albumin from the hydrogels were investigated. The release profiles indicated that both the HPC‐g‐AA and PGH contents played important roles in the drug release behaviors. These results show that the smart hydrogels seem to be of great promise in pH–temperature oral drug delivery systems. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

聚(4-乙酰基丙烯酰乙酸乙酯-co-丙烯酸)水凝胶的溶胀动力学以及温度敏感性研究

通过分子结构设计, 合成了疏水性单体4-乙酰基丙烯酰乙酸乙酯(AAEA), 并以该单体与丙烯酸(AA)进行自由基溶液共聚, 制备了P(AAEA-co-AA)新型温度敏感性水凝胶. AAEA的¹H NMR及FT-IR分析表明, 该单体主要以烯醇式结构存在; P(AAEA-co-AA)的FT-IR分析发现, PAAEA与PAA之间存在较强烈的氢键作用, 使得AAEA烯醇异构体中的C—O伸缩振动吸收峰移向了低波数处. 对冷冻干燥后凝胶的电镜分析发现, 当AAEA用量较高时, 由于凝胶内部分子链段的疏水聚集, 各部分溶胀度以及溶胀速度不均一而使得凝胶表面粗糙不平. 采用DSC对凝胶的体积相转变进行了研究, 结果表明, 该水凝胶的体积相转变温度(VPTT)在48.2至61.8 ℃之间, 并且随着AAEA用量的减小, 凝胶的VPTT逐渐增加. 对该新型温度敏感性水凝胶在去离子水中的溶胀动力学研究发现, 当AAEA用量高于4.6 g时, 凝胶属于Fick凝胶; 反之凝胶则属于非Fick凝胶. 该水凝胶在去离子水中具有良好的温度敏感性, 当外界温度低于VPTT时, 凝胶能保持溶胀状态; 而当外界温度高于VPTT时, 凝胶的平衡溶胀度迅速下降, 表现为温度敏感性. 进一步研究发现, 凝胶组成不仅会影响凝胶的VPTT, 而且会影响凝胶温度敏感性的强弱.     

烷氧磺酸盐功能化的聚乙撑二氧噻吩水凝胶

通过氧化偶联聚合方法成功地制备出一种基于烷氧磺酸盐功能化的聚乙撑二氧噻吩水凝胶, 揭示了零维单体胶束向二维纳米片层及三维水凝胶的转变过程, 发现通过改变反应温度或初始单体浓度, 可以诱导水凝胶网络结构单元的维度变化, 即由零维纳米粒子向二维纳米片层进行转化. 提出了一种导电高分子水凝胶的合成方法, 即采用一种氧化剂与一种多价金属盐的混合物作为引发剂, 其中前者用于诱导单体聚合, 后者则充当离子交联试剂, 并发现可以通过引入不同金属离子来改变凝胶的形貌. 此外, 导电高分子水凝胶具有良好的电化学电容, 并具有选择性吸附与可控脱附某些染料分子的特性.     

Radiation preparation and diffusion behavior of thermally reversible hydrogels

Temperature sensitive PolyNIPAAm hydrogels in the form of rod were prepared from the binary system of NIPAAm/water and ternary system of NIPAAm/Bis/water by γ-irradiation with ⁶⁰Co source at room temperature, respectively. The prepared hydrogels had obvious temperature sensitivity (LCST is about 35.0 °C) and suitable mechanical properties. The incorporation of cross-linking agent, N, N′-methylene-bisacrylamide (Bis), into the binary system of monomer/water reduced the gelation dose. The maximum swelling ratio of hydrogels was decreased with the increasing of dose or the incorporation of Bis. The diffusion behavior of water in hydrogels obtained in this work was investigated. In addition, the drug delivery of fluoro uracili (Fu-5) from the hydrogels was investigated.     

Synthesis of versatile poly(PMMA‐b‐VI) macromonomer‐based hydrogels via infrared laser ignited frontal polymerization

In this work, poly((PMMA‐b‐VI)‐co‐AA) (MMA = methyl methacrylate; VI = 1‐vinylimidazole; AA = acrylic acid) hydrogels and poly((PMMA‐b‐VI)‐co‐AA)/TPU (TPU = thermoplastic polyurethane) IPN (interpenetrating polymer networks) hydrogels have been fabricated via versatile infrared laser ignited frontal polymerization by using poly(PMMA‐b‐VI) macromonomer as the mononer. The frontal velocity and T_max (the highest temperature that the laser beam detected at a fixed point) can be adjusted by varying monomer weight ratios, the concentration of BPO (BPO = benzoyl peroxide) and the amount of TPU. Moreover, the addition of TPU enhances the reactant viscosity to suppress the “fingering” of frontal polymerization (FP) and decrease T_max of the reaction, providing a new inert carrier (TPU) to assist FP. Through the characterization of Fourier transform‐infrared spectroscopy (FT‐IR), scanning electron microscope (SEM), and differential scanning calorimetry (DSC), the desired structure can be proved to exist in the IPN hydrogels. Furthermore, poly((PMMA‐b‐VI)‐co‐AA)/TPU IPN hydrogels possesses more excellent mechanical behaviors than hydrogels without IPN structure. Besides, the poly((PMMA‐b‐VI)‐co‐AA) hydrogels present splendid sensitive properties toward substances of different flavor including sourness (CA, citric acid or GA, gluconic acid), umami (SG, sodium glutamate), saltiness (SC, sodium chloride), sweetness (GLU, glucose), enabling their potential as artificial tongue‐like sensing materials. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1210–1221     

Effect of chemical structure on the properties of some hydrogels prepared by using gamma radiation polymerization

Several hydrogels were prepared using radiolytic polymerization of aqueous solutions of acrylamide or acrylamide containing appropriate comonomer such as acrylic acid, maleic acid, itaconic acid, and maleic anhydride. The hydrogels have been prepared at an irradiation dose of 30 kGy. The effects of the chemical structure of the monomer(s) and crosslinking agents on the yield of homopolymer(s) or copolymers have been studied. These crosslinking agents include N, N′‐methylene dimethacrylate (MDA) and N, N′‐methylene bisallyamide (MBA). The hydrogels obtained were characterized using swelling technique, thermal and spectroscopic analysis. The results obtained showed that the prepared samples are able to reject sodium ions and are not able to recover the Basic Blue Dye from their aqueous solution. © 2005 John Wiley & Sons, Ltd.     

Synthesis and release profile analysis of thermo-sensitive albumin hydrogels

Novel thermo-responsive hydrophilic microspheres were prepared by free radical polymerization of methacrylate bovine serum albumin and N-isopropylacrylamide, as cross-linker and functional monomer, respectively. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and shape of hydrogels strictly depend on concentration of monomers in the polymerization feed. The thermal analyses showed negative thermo-responsive behavior with pronounced water affinity of microspheres at temperature lower than lower critical solution temperature (LCST). The in vitro release studies of drug-loaded thermo-sensitive hydrogels were performed. Experimental data showed, for the copolymers with functional monomer/cross-linker ratio ≤ 1, a predominant drug release in the collapsed state, while the copolymers with functional monomer/cross-linker ratio > 1 showed prominent drug release in the swollen state. Below the hydrogel LCST, drug release through the swollen polymeric networks was observed, while a squeezing-out effect at temperature above the LCST was predominant.     

Synthesis and properties of pH and temperature sensitive P(NIPAAm-co-DMAEMA) hydrogels

In order to investigate the influence of the continuous alkylamide sequence having pH sensitive unit on the temperature sensitivity of poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogel, a monomer, N-(2-(dimethylamino) ethyl)-methacrylamide (DMAEMA), having an ethylamide group as well as an aliphatic tertiary amino group, was designed and synthesized. Hydrogels based on NIPAAm and DMAEMA were prepared via free radical polymerization. The resulted P(NIPAAm-co-DMAEMA) hydrogels were characterized in terms of maximum swelling ratio, swelling kinetics, temperature response kinetics, and effect of pH. The data obtained show that the novel hydrogels have the strong desire to respond to external temperature and pH stimuli. Importantly, because the P(NIPAAm-co-DMAEMA) hydrogels have the continuous alkylamide sequence containing isopropylamide pendant groups from PNIPAAm and ethylamide pendant groups from PDMAEMA, the incorporation of DMAEMA moiety not only provides the pH sensitivity, but also maintains the thermal properties of P(NIPAAm-co-DMAEMA) hydrogels, even as the molar percentage of DMAEMA moiety reaches 14 mol%.     

Novel pH‐sensitive polymers containing sulfonamide groups

Novel pH‐sensitive polymers were synthesized by copolymerizing a monomer derivatized from 4‐amino‐N‐[4,6‐dimethyl‐2‐pyrimidinyl]benzene sulfonamide with N,N‐dimethylacrylamide. The linear copolymers showed pH‐sensitive solubility, while chemically crosslinked hydrogels exhibit a relatively sharp transition in swelling around physiological pH. These changes were found to be reversible. By varying the type of sulfonamide and the copolymer composition, a new class of pH‐sensitive polymers with a broad range of transition pH can be synthesized.     

Using hydrophobic additive as pore‐forming agent to prepare macroporous PNIPAAm hydrogels

Hydrophobic poly(lactic acid) nanospheres were fabricated and used as an additive during the polymerization and gelation process of temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels. The influence of hydrophobic additive on properties of PNIPAAm hydrogels was examined. The interior morphology studied by scanning electron microscopy revealed that the hydrophobic additive induced a macroporous structure in the resulting PNIPAAm hydrogels. Results demonstrate that the hydrophobic additive acts as a pore‐forming agent like conventionally used hydrophilic additive does during the gelation process. Because of the macroporous network and incorporated additives, the temperature‐sensitive characteristics, particularly the equilibrium swelling ratio at room temperature and shrinking rate upon temperature increase of modified PNIPAAm hydrogels, are significantly improved. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5490–5497, 2005     

Selective enrichment and separation of phosphotyrosine peptides by thermosensitive molecularly imprinted polymers

Novel thermosensitive molecularly imprinted polymers were successfully prepared using the epitope imprinting approach in the presence of the mimic template phenylphosphonic acid, the functional monomer vinylphosphonic acid‐Ti⁴⁺, the temperature‐sensitive monomer N‐isopropylacrylamide and the crosslinker N,N′‐methylenebisacrylamide. The ratio of the template/thermosensitive monomers/crosslinker was optimized, and when the ratio was 2:2:1, the prepared thermosensitive molecularly imprinted polymers had the highest imprinting factor. The synthetic thermosensitive molecularly imprinted polymers were characterized by Fourier transform infrared spectroscopy to reveal the combination and elution processes of the template. Then, the adsorption capacity and thermosensitivity was measured. When the temperature was 28°C, the imprinting factor was the highest. The selectivity and adsorption capacity of the thermosensitive molecularly imprinted polymers for phosphotyrosine peptides from a mixture of three tailor‐made peptides were measured by high‐performance liquid chromatography. The results showed that the thermosensitive molecularly imprinted polymers have good selectivity for phosphotyrosine peptides. Finally, the imprinted hydrogels were applied to specifically adsorb phosphotyrosine peptides from a sample mixture containing phosphotyrosine and a tryptic digest of β‐casein, which demonstrated high selectivity. After four rebinding cycles, 78.9% adsorption efficiency was still retained.     

A novel method to prepare temperature/pH‐sensitive poly(N,N‐diethylacrylamide‐co‐acrylic acid) hydrogels with rapid swelling/deswelling behaviors

Fast responsive temperature‐ and pH‐sensitive hydrogels of poly(N,N‐diethylacrylamide‐co‐acrylic acid) (P(DEA‐co‐AA)) have been synthesized successfully by a two‐step procedure, in which the initial polymerization was conducted at constant temperature for 15 min, followed by further polymerization at ?30°C for 12 hr. Swelling studies showed that hydrogels thus prepared had almost the same temperature and pH sensitivity compared with the conventional ones (polymerized at 24°C for 12 hr). However, hydrogels thus prepared had faster swelling/deswelling rates in distilled water than the conventional ones, and their deswelling rates in low pH buffer solutions were also faster than the conventional ones. These improved properties were attributed to the porous network structure, which was confirmed by the results of scanning electron microscopy. Copyright © 2009 John Wiley & Sons, Ltd.     

Comparative rheological study of ionic semi-IPN composite hydrogels based on polyacrylamide and dextran sulphate and of polyacrylamide hydrogels

Ionic semi-interpenetrating polymer networks composite hydrogels were synthesized by free-radical polymerization using dextran sulphate (DxS), acrylamide as monomer and N,N′-methylene(bis)acrylamide as cross-linking agent. The viscoelastic properties of these composite hydrogels were investigated by oscillatory shear measurements under small deformation conditions comparative with those of polyacrylamide gels. Changes of the rheological properties of composite hydrogels have been studied in terms of polymerization temperature, cross-linker ratio, initial monomer concentration and molar mass of DxS. The results showed that the stability of the composite hydrogels obtained at room temperature (22?°C) was relatively low because the storage modulus (G′) was only eight times higher than the loss modulus (G″), while for those obtained by cryopolymerization (?18?°C), the stability was improved, the G′ values being about 30 times higher than those of G″. This behaviour indicated that, by conducting the synthesis of hydrogels below the freezing point of the reaction solutions, an enhancement of the hydrogels elasticity was achieved. The network parameters, i.e. the average molecular weight between two cross-links and the cross-link density of the composite hydrogels prepared at ?18?°C, were estimated from rheological data.