The effect of preparation temperature on the swelling behavior of poly (N-isopropylacrylamide) gels

Summary The role of the preparation temperature of poly(N-isopropylacrylamide) (PNIPA) gels on their swelling behavior in water and in aqueous solutions of sodium dodecylbenzenesulfonate was investigated. PNIPA gels were prepared by free-radical crosslinking copolymerization of N-isopropylacrylamide and N,N'-methylene(bis) acrylamide in water at fixed monomer and crosslinker concentrations. The equilibrium swelling ratio of the gels increases first slightly up to about 20°C then rapidly with increasing gel preparation temperature. Magnitude of the collapse transition in water at 34°C becomes larger as the gel preparation temperature increases. Calculations indicate a decrease in the effective crosslink density of PNIPA gels with increasing preparation temperature. The gels prepared at temperatures higher then 20°C were heterogeneous consisting of highly crosslinked regions interconnected by the PNIPA chains. Received: 3 May 2000/Revised version: 3 July 2000/Accepted: 17 July 2000     

Synthesis of porous poly(N‐isopropylacrylamide) gel beads by sedimentation polymerization and their morphology

Sedimentation polymerization of aqueous solutions of N‐isopropylacrylamide (NIPA) was carried out to prepare porous poly(N‐isopropylacrylamide) (PNIPA) beads. When small amounts of DMF and a radical accelerator were added to the monomer solution, the polymerization proceeded smoothly to give polymer beads with a very narrow size distribution. The rate of swelling of the resulting bead increased with increasing crosslinker content and was also affected by the type of crosslinker used. When amounts higher than 1 mol % N,N′‐methylenebisacrylamide or 3 mol % diethylene glycol diacrylate (DEGDA) were used as a crosslinker, the resulting beads underwent rapid swelling in water at 20°C, reaching the equilibrium within 5 min. A cross‐sectional photograph of a typical dried bead showed that it had a very complex morphology consisting of a large and irregular void, highly porous region, and nonporous region. The swelling rate was directly dependent on the morphology of the beads. PNIPA beads with well‐developed porous areas show a high swelling rate. Although PNIPA beads produced from DEGDA had well‐developed porous structures, they were able to effectively concentrate blue dextran from the dilute aqueous solution. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 842–850, 2007     

一种温敏性水凝胶复性体系:聚N-异丙基丙烯酰胺的制备及其在溶菌酶复性中的应用

Temperature-sensitive hydrogel-poly(N-isopropyl acrylamide) (PNIPA) was prepared and applied to protein refolding. PNIPA gel disks and gel particles were synthesized by the solution polymerization and inverse suspension polymerization respectively. The swelling kinetics of the gels was also studied. With these prepared PNIPA gels, the model protein lysozyme was renatured. Within 24 h, PNIPA gel disks improved the yield of lysozyme activity by 49.3% from 3375.2 U.mg-1 to 5038.8 U.mg-1. With the addition of faster response PNIPA gel beads,the total lysozyme activity recovery was about 68.98% in 3h, as compared with 42.03% by simple batch dilution.The novel refolding system with PNIPA enables efficient refolding especially at high protein concentrations. Discussion about the mechanism revealed that when PNIPA gels were added into the refolding buffer, the hydrophobic interactions between denatured proteins and polymer gels could prevent the aggregation of refolding intermediates,thus enhanced the protein renaturation.     

Swelling–shrinking hysteresis of poly(N‐isopropylacrylamide) gels in sodium dodecylbenzenesulfonate solutions

The swelling and shrinking behaviors of a series of poly(N‐isopropylacrylamide) (PNIPA) hydrogels are studied in aqueous solutions of sodium dodecylbenzenesulfonate (SDBS). Between 0 and 3 mol % 2‐acrylamido‐2‐methylpropanesulfonic acid sodium salt (AMPS) is used as an ionic comonomer in the hydrogel synthesis. It is shown that the collapsed PNIPA gels in water at 52°C start to swell above a critical SDBS concentration in the external solution. This critical concentration decreases as the ionic group content of PNIPA gel increases. A comparison of the swelling and shrinking experiments in SDBS solutions indicates strong hysteresis behavior of PNIPA gels. A more diluted solution is required to make a swollen gel start to reshrink than to cause gel swelling. The results show strong attractive forces between the isopropyl groups of the PNIPA network and the DB groups of SDBS molecules. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1228–1232, 2002     

Reentrant phase transition of poly(N‐isopropylacrylamide) gels in polymer solutions: Thermodynamic analysis

The swelling behavior of poly(N‐isopropylacrylamide) (PNIPA) gels in polymer solutions, particularly in aqueous solutions of poly(ethylene glycol)s, was investigated using the theory of equilibrium swelling. The volume of the PNIPA gel and the partition parameter of the macromolecules between the gel and the solution phases were calculated for various extents of the energetic interactions between the components. The simulation results were compared with the experimental data reported in the literature. It was shown that the PNIPA gel has a tendency to a reentrant phase transition in an aqueous solution of low molecular weight linear polymers. In such a transition, the gel first collapses, then reswells, if the linear polymer concentration is continuously varied. The necessary condition for the reentrant behavior of PNIPA gels was predicted in terms of the interaction parameters among the PNIPA network, the linear polymer, and water. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 801– 813, 2002     

Synthesis and characterization of thermally-responsive hydroxypropyl methylcellulose gel beads

Thermally responsive gels of hydroxypropyl methylcellulose (HPMC) were produced in spherical form by a suspension crosslinking technique. The suspension crosslinking of HPMC with divinylsulfone was accomplished by dispersing aqueous polymer droplets, containing all of the reactants, in a continuous organic phase. The gel beads were characterized in terms of their swelling properties and particle size distribution. The swelling degrees at 25°C of different formulations of the gel beads ranged from 12 to 123 times their dry volume and shrank to 4 to 18 times dry volume at 75°C. The spherical beads were made in diameters ranging from 500 to 3000 μ. Bead size generally decreased with use of a larger impeller, suspending at high stirring speeds, or at a lower phase ratio. As bead size decreased, the size distribution also narrowed. When compared with bulk HPMC gels, the gel beads demonstrated the same swelling properties and crosslinked network formation. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1279–1290, 1997     

Thermosensitive poly(N‐isopropylacrylamide) hydrogel for refolding of recombinant bovine prethrombin‐2 from E. coli inclusion bodies

The poly(N‐isopropylacrylamide) (PNIPA) hydrogel, which is a kind of temperature‐sensitive polymer, was synthesized by inverse suspension polymerization. The microscopy and scan electron microscopy (SEM) of PNIPA hydrogel were studied. The microscope photograph showed that the particles were in the range of 0.2–0.5mm in diameter, with numerous conjoint pores about 1–2μm spreading all over the surface of the beads. The swelling properties of PNIPA gel beads indicated that the lower critical solution temperature (LCST) of the gel was 33°C. The PNIPA prepared was applied to the renaturation of bovine prethrombin‐2 (pThr‐2) from inclusion bodies produced in E. coli. It was observed that PNIPA was quite efficient in assisting protein renaturation at high protein concentration. When mixing with 105mg/mL PNIPA hydrogel during the refolding, the total activity of the thrombin was about 6222U/mL, compared with only 2800U/mL by simple dilution refolding. The kinetics of pThr‐2 refolding with the absence or the presence of PNIPA was also studied respectively. The time required for the refolding with PNIPA gel was a little bit longer than that by the dilution method owing to the diffusion resistance of the protein into the network of the gel and the hydrophobic interaction between the protein and the polymer. The mechanism of the enhancement for the PNIPA gel to the refolding was further discussed. The porosity of the PNIPA hydrogel allows penetration of the unfolded protein into the inside of the polymer with a hydrophobic side chain, which can facilitate the formation of intermediate via hydrophobic interaction with the unfolded protein and the folding intermediate that are liable to re‐aggregation. About 1.2mg of purified active thrombin could be recovered from 1 L of cells, which greatly facilitated the scale‐up to the quantities of protein necessary for further functional and structural studies. A novel protein renaturation method mediated by PNIPA hydrogel beads, which highly increases the refolding efficiency with easy handling, recycling, and low cost, was proposed. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1734–1740, 2005     

Thermoreversible hydrogels. IV. Effect of some factors on the swelling behavior of N-tetrahydrofurfurylacrylamide

A thermoreversible hydrogel, poly(N-tetrahydrofurfurylacrylamide) [poly-(NTHFAAm) gel], was prepared from N-tetrahydrofurfurylacrylamide, which was synthesized from N-tetrahydrofurfurylamine and acryloyl chloride (through acylation), with N,N′-methylenebisacrylamide, a crosslinker, in various aqueous solutions. The influences of temperature, gel thickness, and polymerization media on the swelling behaviors in water were investigated. The effect of the gel thickness on the swelling ratio for NTHFAAm gel indicated that the equilibrium swelling time and diffusion coefficient for the thinner gel were faster than those for the thicker gels. The effects of different polymerization media on the gel swelling ratio showed that the larger the solvent molecular size and the poorer the miscibility of the monomer and solvent, the higher the swelling ratio and diffusion coefficient. The drug release profiles in the various gels were also investigated. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 68: 1597–1603, 1998     

Swelling behavior of physical and chemical DNA hydrogels

DNA hydrogels were prepared from aqueous solutions of double‐stranded DNA (about 2000 base pairs long) by physical and chemical means. Physical gels were obtained via denaturation–renaturation cycle of 5% aqueous DNA solutions between 25 and 90°C. Although physical DNA gels exhibit a high modulus of elasticity, the crosslinks holding the DNA network together are destroyed during the expansion of gels in water or in dilute salt solutions. It was shown that these gels can be used for the controlled release of DNA in aqueous media. Chemical DNA gels formed using ethylene glycol diglycidyl ether crosslinker are stable in water with a wide range of swelling ratios that could be adjusted by the amount of DNA at the gel preparation. Swelling behavior of chemical DNA gels in acetone/water mixtures as well as in aqueous salt solutions is very similar to that of synthetic polyelectrolyte hydrogels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis of porous poly[oligo(ethylene glycol) methyl ether methacrylate] gels that exhibit thermosensitivity in highly concentrated aqueous NaCl solution

The polymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) in 20 wt% aqueous ethanol solution and oligo(ethylene glycol) methyl ether methacrylate (OEGMA₃₀₀, M_n = 300 g mol^?1) in water was carried out in the presence of a crosslinker. Polymerization at temperatures above the lower critical solution temperature (LCST) yielded the corresponding porous poly[oligo(ethylene glycol) methyl ether methacrylate] gels by polymerization-induced phase separation. The resulting porous gels showed rapid swelling-deswelling in water. The temperature dependency of the equilibrium swelling ratio of the gels was investigated in several concentrated aqueous NaCl solutions. At 20 °C, the equilibrium swelling ratios of the POEGMA₃₀₀ gel obtained from OEGMA₃₀₀ were largely unaffected by NaCl concentration; however, above 30 °C, they decreased with increasing NaCl concentration. Therefore, the POEGMA₃₀₀ gel showed sharp and high thermosensitivity in highly concentrated aqueous NaCl solutions. Similar swelling behaviors were observed for PMEO₂MA gel, which was prepared from MEO₂MA.     

Uniform poly(isopropylacrylamide) gel beads for immobilization of α-chymotrypsin

In this study, α-chymotrypsin was immobilized via physical entrapment within large, uniformly spherical, and thermally reversible poly(N-isopropylacrylamide) [poly(NIPAM)] beads. The gel beads were prepared in an aqueous dispersion medium by using Ca-alginate gel as the polymerization mold. In this preparation, potassium persulfate/tetramethylethylenediamine and sodium-alginate/calcium chloride were used as the redox initiator and the stabilizer systems, respectively. Thermoresponsive poly(NIPAM) gel beads 3 mm in size and including α-chymotrypsin were produced by the proposed procedure. The use of an aqueous bead-forming medium did not cause significant enzyme leakage during the preparation of enzyme-gel beads. Michaelis–Menten kinetics was used to define the behaviors of enzyme-gel beads prepared with different enzyme loadings. The Lineweaver–Burk plot indicated that the enzyme-gel system had a reasonably higher K_m value relative to that of free enzyme due to the internal mass transfer resistance against the substrate diffusion. The enzyme-gel system exhibited the maximum activity at 30°C due to the thermoresponsive character of the carrier matrix. However, the maximum activity with the free enzyme was observed at 40°C. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 67:1127–1139, 1998     

Radiation polymerization and concentration separation of P(NIPA‐co‐AMPS) hydrogels

Extraction or concentration with temperature‐sensitive hydrogels is a novel separation technology. In this study, N‐isopropylacrylamide (NIPA) was synthesized by acrylonitrile and isopropanol. Poly(N‐isopropylacrylamide) (PNIPA) and copolymer of NIPA and 2‐acrylamide‐2‐methylpropane sulfonate [P(NIPA‐co‐AMPS)] hydrogels were prepared by radiation polymerization. Dependence of their swelling behavior on temperature was studied. Effects of radiation dose on polymerization, feed composition on thermoresponse, electrolyte on relative swelling ratio, and swelling and deswelling kinetics were investigated. The experimental results showed that P(NIPA‐co‐AMPS) hydrogels with low content of AMPS/NIPA (1–5 %), prepared at a radiation dose‐rate of 1 kGy/h and total dose of 30–40 kGy, could enhance the swelling ratio of PNIPA hydrogels significantly and raise the phase‐transition temperatures. P(NIPA‐co‐AMPS) hydrogels produced under optimum conditions were used to concentrate aqueous bovine serum albumin (BSA, M = 69 000 g mol^?1) solution. When aqueous BSA concentration was below 5 %, the separation efficiency was more than 80 % with low cost and low energy consumption. Copyright © 2005 Society of Chemical Industry     

温敏型聚合物PNIPA和P(NIPA-co-SA)的制备及其协助溶菌酶复性研究

采用反相悬浮法合成了温敏型聚合物聚N-异丙基丙烯酰胺(PNIPA)凝胶及其与丙烯酸钠(SA)的共聚凝胶P(NIPA-co-SA),对凝胶的形态、粒径分布、表面特性以及温敏性能进行了考察,共单体丙烯酸钠的引入使得凝胶的最大溶胀倍率和低临界溶解温度(LCST)都有明显的提高。将两种凝胶用于目标蛋白溶菌酶的体外复性过程,考察了其协助复性的效果。结果表明:当蛋白浓度为250μg·mL-1时,加入80mg·mL-1PNIPA凝胶可使溶菌酶的活性回收率由稀释复性的51.3%提高到72.9%;加入120mg·mL-1P(NIPA-co-SA)共聚凝胶可使活性回收率达到71.5%。溶菌酶的浓度越高,与稀释复性相比凝胶协助复性的效果就越好。复性后凝胶可方便地分离回收,PNIPA凝胶重复使用6次后,溶菌酶的活性回收率仍高于稀释复性15%以上。     

Volume phase transition in poly(N‐isopropylacrylamide) gels in seawater at high pressures

The swelling behavior of poly(N‐isopropylacrylamide) (PNIPA) gels in seawater at high pressures up to ～40 MPa is examined in terms of human activity at deep sea. The neutral gel in seawater undergoes a continuous volume transition at 26°C at atmospheric pressure. Addition of the ionic group (sodium acrylate) does not have much effect on the swelling properties of the gels in seawater except that the transition temperature is somewhat increased. At high constant pressures up to ～40 MPa, the gels undergo a continuous volume transition at 26–28°C as the temperature varies. Normally, the gel takes a swollen state at deep sea. The ratio of the volume change associated with the transition is more than 10, which is 3 times larger than that obtained by changing the pressure at a constant temperature. The results suggest a possibility that the phase transition of PNIPA gels is utilized for producing mechanochemical energy at deep sea. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 95: 1069–1072, 2005     

Real‐time temperature and photon transmission measurements for monitoring phase separation during the formation of poly(N‐isopropylacrylamide) gels

Phase separation during the formation of poly(N‐isopropylacrylamide) (PNIPA) hydrogels was investigated using real‐time photon transmission and temperature measurements. The hydrogels were prepared by free‐radical crosslinking polymerization of N‐isopropylacrylamide (NIPA) in the presence of N,N′‐methylenebisacrylamide (BAAm) as a crosslinker in an aqueous solution. The onset reaction temperature T₀ was varied between 20 and 28°C. Following an induction period, all the gelation experiments resulted in exothermic reaction profiles. A temperature increase of 6.5 ± 0.6°C was observed in the experiments. It was shown that the temperature increase during the formation and growth process of PNIPA gels is accompanied by a simultaneous decrease in the transmitted light intensities I_tr. The decrease in I_tr at temperatures below the lower critical solution temperature of PNIPA was explained by the concentration fluctuations due to the inhomogeneity in the gel network. At higher temperatures, it was shown that the gel system undergoes a phase transition via a spinodal decomposition process. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3589–3595, 2002     

pH‐sensitive uniform gel beads for DNA adsorption

Uniform gel beads 3 mm in diameter were obtained by the suspension polymerization of an amine functionalized monomer, N‐3‐(dimethyl amino)propylmethacrylamide (DMAPM). The polymerization of DMAPM in the form of uniform droplets could be achieved at room temperature in an aqueous dispersion medium by using Ca–alginate gel as the polymerization mold. In this preparation, potassium persulfate/tetramethyl ethylenediamine and sodium alginate/calcium chloride were used as the redox initiator and the stabilizer systems, respectively. The crosslinked DMAPM gel beads exhibited pH‐sensitive, reversible swelling–deswelling behavior. The uniform gel beads were also obtained by the copolymerization of DMAPM and acrylamide (AA) in the same polymerization system. Although copolymer gel beads with higher pH sensitivities were obtained with increasing feed concentration of DMAPM, the total monomer conversion decreased. Crosslinked DMAPM and DMAPM–AA copolymer gel beads were utilized as sorbents for DNA adsorption. The gel beads produced with higher DMAPM feed concentration exhibited higher equilibrium DNA adsorption capacity. The DNA equilibrium adsorption capacities up to 50 mg DNA/g dry gel could be achieved with the crosslinked DMAPM gel beads. This value was reasonably higher relative to the previously reported adsorption capacities of known sorbents. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 3154–3161, 2000     

Preparation of ketoprofen‐loaded high‐molecular‐weight poly(vinyl alcohol) gels

High‐molecular‐weight atactic poly(vinyl alcohol) (a‐PVA) gels loaded with (R,S)‐2‐(3‐benzoylphenyl)propionic acid (ketoprofen) were prepared from 5, 6, 7, and 8 g/dL solutions of a‐PVA with a number‐average degree of polymerization of 4000 in an ethylene glycol/water mixture with an aging method to identify the effect of the initial polymer concentration on the swelling behavior, morphology, and thermal properties of a‐PVA gels. Then, the release behavior of ketoprofen from a‐PVA gels was investigated. As the polymer concentration decreased, the ability for network formation decreased, and the degree of swelling of the a‐PVA gels increased. In addition, the enthalpy increased with an increase in the a‐PVA concentration, but the melting temperatures of the gels prepared at different initial polymer concentrations were the same; this indicated that tighter gel networks would be formed by a higher polymer chain density. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Tremendous reinforcing,pore‐stabilizing and response‐accelerating effect of in situ generated nanosilica in thermoresponsive poly(N‐isopropylacrylamide) cryogels

The tremendous reinforcing and pore‐stabilizing effect of in situ formed nanosilica in a highly porous temperature‐responsive poly(N‐isopropylacrylamide) (PNIPA) matrix is demonstrated. A very weakly crosslinked semi‐liquid hydrogel can be reinforced to the point that it displays a fast, extensive and nearly symmetric temperature‐responsiveness in combination with an acceptable modulus. In soft but solid porous PNIPA, only 0.6 wt% of the nanofiller is sufficient to stabilize the pores against collapse upon de‐swelling, thus enabling ultrafast responsiveness. A spectacular effect is achieved with dried porous PNIPA (matrix is glassy, T_g ≈ 140 °C), which in the case of optimal nanosilica amounts can re‐swell in only 3 min. The key importance of efficient hydrogen bridging between PNIPA and SiO₂ is demonstrated by comparing in situ formed nanosilica with similarly sized commercial Ludox particles, the surface of which is saturated with ammonia (for stabilization). Synthesis parameters like the amount of crosslinker and of nanosilica were varied in a wide range, in order to achieve the fastest possible responsiveness of the hydrogels in combination with a high modulus. The porosity, nanosilica distribution, moduli, temperature‐dependent swelling as well as the swelling kinetics of the gels were determined as functions of contents of crosslinker and nanosilica. © 2017 Society of Chemical Industry     

Network parameters and volume phase transition behavior of poly(N‐isopropylacrylamide) hydrogels

Thermosensitive hydrogels were prepared by free radical polymerization in aqueous solution from N‐isopropylacrylamide (NIPA) monomer and N,N‐methylenebis(acrylamide) (MBAAm) crosslinker. The swelling equilibrium of the hydrogels in deionized water was investigated as a function of temperature and MBAAm content. The results indicated that the swelling behavior and temperature sensitivity of the hydrogels were affected by the amount of MBAAm content. The average molecular mass between crosslinks and polymer–solvent interaction parameter (χ) of the hydrogels were determined from equilibrium swelling values. The swelling variations were explained according to swelling theory based on the hydrogel chemical structure. The swelling equilibrium of the hydrogels was also investigated as a function of temperature in aqueous solutions of the anionic surfactant sodium dodecyl sulfate (SDS) and the cationic surfactant dodecyltrimethylammonium bromide (DTAB). In deionized water, the hydrogels showed a discontinuous volume phase transition at 32°C. In SDS and DTAB solutions, the equilibrium swelling ratio and the volume phase transition temperature (lower critical solution temperature) of the hydrogels increased, which is ascribed to the conversion of nonionic PNIPA hydrogel into polyelectrolyte hydrogels because of binding of surfactant molecules through the hydrophobic interaction. Additionally, the amount of free SDS and DTAB ions was measured at different temperatures by a conductometric method; it was found that the electric conductivity of the PNIPA–surfactant systems depended strongly on both the type and concentration of surfactant solutions. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1756–1762, 2006     

Macroporous poly(N-isopropylacrylamide) networks

Summary Effects of the gel preparation temperature T _prep and the initial monomer concentration c on the swelling and the porosity properties of poly(N-isopropylacrylamide) (PNIPA) networks are described. PNIPA networks were prepared by free-radical crosslinking copolymerization of N-isopropylacrylamide and N,N'-methylene(bis)acrylamide (BAAm) in aqueous solutions. The crosslinker (BAAm) concentration in the initial monomer mixture was kept constant at 30 wt %. It was shown that macroporous PNIPA networks with a stable porous structure can be prepared at T _prep = 22.5°C and at an initial monomer concentration c > 5 w/v %. The PNIPA networks contain pores of about 0.1 μm in radius, corresponding to the interstices between the microspheres. The experimental data also show collapse of the porous structure in PNIPA networks formed at higher temperatures. Received: 30 January 2002 / Revised version: 16 May 2002 / Accepted: 1 June 2002