Equilibrium swelling behavior of thermally responsive metal affinity hydrogels, Part I: Compositional effects

Copolymer hydrogels were synthesized from N-isopropylacrylamide (NIPAAm) and vinyl iminodiacetic acid (VIDA) monomers, incorporating thermally responsive swelling and metal affinity properties. Compared to pure NIPAAm hydrogels, the copolymer hydrogels showed significantly increased swelling due to the hydrophilic VIDA groups while still retaining their sharp phase transition behavior. However, excessive amounts of VIDA caused the gels to lose this behavior and not fully collapse even at temperatures as high as 80 °C. When chelated with copper the VIDA groups became less hydrophilic, partially reversing the increased swelling due to VIDA, enabling the gels to regain their phase transition behavior. Increasing the crosslinking density in the gels generally had the effect of decreasing their swelling. However, for gels with higher VIDA amounts, increasing the crosslinking density unexpectedly caused the hydrophilic groups with bound waters to resist the hydrophobic group-induced collapse at high temperatures. The results suggest that the NIPAAm, VIDA and crosslinker amounts and copper chelation are essential elements in the molecular design of the gel to retain a sharp phase transition. These variables were used to develop a phase transition phase diagram.     

Kinetics and mechanisms of water sorption in hydrophobic,ionizable copolymer gels

The aqueous kinetic swelling properties of a class of cross-linked hydrophobic polyamine copolymer gels based on n-alkyl esters of methacrylic acid (nAMA) and N,N-dimethylaminoethyl methacrylate (DMA) have been studied as a function of solution ionic composition (pH, ionic strength, and buffer content), gel composition, and temperature. Water uptake and swelling in these gels are driven by ionization of the DMA amine groups, which overcomes the hydrophobic tendency of these gels to exclude water in the unionized state. Sorption kinetics in initially glassy gel disks are generally biphasic, characterized by an initial phase of relatively slow water uptake followed by an accelerated phase during which significant volume expansion of the gel occurs. This sorption/swelling behavior strongly suggests a moving penetrant front mechanism. The initial rate of water sorption increases markedly as (1) solution pH decreases, (2) gel nAMA comonomer content decreases, (3) gel nAMA side-chain length decreases, and (4) temperature increases. Furthermore, the initial phase of sorption in initially glassy gels is generally non-Fickian and approaches zero-order behavior as (1) pH increases, (2) nAMA content increases, and (3) temperature decreases. In direct contrast, sorption in initially dry, rubbery gels is monophasic, but non-Fickian, and approaches zero-order behavior as temperature increases. This behavior is contrary to the Fickian sorption behavior normally observed in polymers above their glass transition temperatures. Finally, sorption kinetics critically depend upon the nature of the ions in solution: Kinetics are significantly faster in the presence of weak electrolytes than that of strong electrolytes. We discuss the importance of the rate of ion transport in determining the overall sorption kinetics and how sorption kinetics can be non-Fickian in rubbery gels. Also, we propose a mechanism for the observed enhanced kinetics in the presence of weak electrolytes.     

Thermoreversible hydrogel. V. Synthesis and swelling behavior of the N-isopropylacrylamide-co-trimethyl methacryloyloxyethyl ammonium iodide copolymeric hydrogels

A series of N-isopropylacrylamide/trimethyl methacryloyloxyethyl ammonium iodide (NIPAAm/TMMAI) copolymeric gels are prepared from the various molar ratios of NIPAAm, cationic monomer TMMAI, and N,N′-methylene bisacrylamide (NMBA) in this article. The influences of the amount of the cationic monomer in the copolymeric gels on the swelling behavior in water, various saline solutions, and various temperatures are investigated. Results show that the swelling ratios of copolymeric gels are significantly larger than those of pure homopolymer NIPAAm gel, and the more the TMMAI content, the higher the gel transition temperature. In the saline solution, results show that the swelling ratio of pure NIPAAm gel has not significantly changed with an increase of the salt concentration until the salt concentration is larger than 0.1M. The swelling ratios for the copolymeric gels NIPAAm/TMMAI decrease with increasing salt concentration. In various saline solutions, results show that the anionic effects are greater than cationic effects in the presence of common anion, different cations and common cation, and different anions for these hydrogels. Finally, we also tested the reversibility of the NIPAAm/TMMAI copolymeric gels. The deswelling and reswelling kinetics are dependent on the temperature, which is below or above the gel transition temperature. The gel with little TMMAI content has a good reversibility. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 1793–1803, 1998     

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     

Thermoreversible hydrogels VI: Swelling behavior of the (N-isopropylacrylamide-co-diethyl methyl methacryloyloxyethyl ammonium iodide) copolymeric hydrogels in aqueous salt solutions

A series of N-isopropylacrylamide/diethyl methyl methacryloyloxyethyl ammonium iodide (NIPAAm/DEMMAI) copolymeric gels were prepared from blending NIPAAm, cationic monomer DEMMAI, and N,N′-methylene bisacrylamide (NMBA) in various molar ratios in this article. The effects of the amount of the cationic monomer in the copolymeric gels on the swelling behaviors in water and various saline solutions at various temperatures were investigated. Results showed that the swelling ratios of copolymeric gels were significantly larger than those of pure NIPAAm gel, and that the more the DEMMAI content, the higher the gel transition temperature. In the saline solution, results showed that the swelling ratio for pure NIPAAm gel had not changed significantly with an increase of the salt concentration until the salt concentration was larger than 0.1 M. The swelling ratios for the copolymeric gels NIPAAm/DEMMAI were decreased with increasing salt concentration. In various saline solutions, results showed that the anionic effects were greater than cationic effects in the presence of common anion with different cations and common cation with different anions for these hydrogels. Finally, we also tested the reversibility of the NIPAAm/DEMMAI copolymeric gels. The deswelling and reswelling kinetics were dependent on the temperature which was below or above the gel transition temperature. The gel with a small DEMMAI content has a good reversibility.     

Thermoreversible Hydrogels XVI: Synthesis and Swelling Behaviors of [N-Isopropylacrylamide–co-trimethyl acrylamidopropyl ammonium iodide-co-3-dimethyl (methacryloxyethyl) ammonium propane sulfonate] Copolymeric Hydrogels in Aqueous Salt Solution

A series of copolymeric hydrogels were prepared from various molar ratios of N-isopropylacrylamide (NIPAAm), trimethyl acrylamidopropyl ammonium iodide (TMAAI), and 3-dimethyl (methacryloxyethyl) ammonium propane sulfonate (DMAPS). The swelling behaviors of these copolymeric hydrogels were investigated in various saline solutions. The result showed that the phase transition temperatures of these gels changed insignificantly, and the thermosensitivity, in contrast, diminished. In the saline solution, results showed that the swelling ratio of pure NIPAAm gel did not significantly change with an increase in the salt concentration until the salt concentration was larger than 0.5 M. In addition, the copolymer gels exhibited polyelectrolytic behavior under lower salt concentration (10^–5–10^–1 M), exhibited a nonionic gel (like NIPAAm) behavior at the salt concentration from 0.1 to 0.5 M, and showed an antipolyelectrolytic behavior (polyzwitterionic effect) at a concentration of salt over 0.5 M.     

pH/thermoreversible hydrogels III: Synthesis and swelling behaviors of (N-isopropylacrylamide-co-acrylic acid) copolymeric hydrogels

A series of pH-thermoreversible hydrogels exhibiting volume phase transition were synthesized by three degrees of neutralization (DN) of acrylic acid (AA) and N-isopropylacrylamide (NIPAAm). The influence of environmental conditions, such as temperature and pH, on the swelling behavior of these copolymeric gels is investigated in this article. Results show that the negatively charged hydrogels exhibit different equilibrium swelling ratios at different pH values depending on the ionic composition. The pH-sensitivities of these gels also strongly depend on the DN of AA in the copolymeric gels. The results show that the higher the DN, the higher the gel pH-sensitivity. These hydrogels based on a temperature-sensitive hydrogel demonstrate a larger change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a collapsed dehydrated network in response to a variation of temperature. On the other hand, a significant phenomenon that was found in the gel swelling kinetics was an overshooting under high temperature conditions. The presented hydrogels were used for release of model drugs that occur at the changes of surrounding conditions, such as temperature and pH, in this study. It was also found that the higher the DN of AA, the higher the gel transition temperature and the larger the release in a high temperature environment and, at the same time, the larger the swelling ratios.     

Thermoreversible swelling behaviour of hydrogels based on N-isopropylacrylamide with a hydrophobic comonomer

Hydrogels were prepared by free radical polymerisation in aqueous solution of N-isopropylacrylamide (NIPA) and of NIPA with di-n-propylacrylamide (DPAM), di-n-octylacrylamide (DOAM) or di-dodecylacrylamide (DDAM) as hydrophobic comonomer. N,N-methylene bisacrylamide (BIS) and glyoxal bis(diallyacetal) (GLY) were used as crosslinkers. A series of copolymers with three different comonomer contents was synthesised and for some polymers three different crosslinker concentrations were employed. The swelling equilibrium of these hydrogels was studied as a function of temperature, hydrophobic comonomer species and content in aqueous solutions of the anionic surfactant sodium dodecyl sulfate (SDS). In pure water the gels showed a discontinuous volume phase transition at 33 and 30 °C for PNIPA and hydrophobically modified PNIPA copolymeric hydrogels, respectively. The swelling ratio r and the transition temperature (LCST) increased at low temperatures with the addition of SDS, this is ascribed to the conversion of non-ionic PNIPA gels into polyelectrolyte gels through the binding of SDS. At SDS concentration below 0.5 wt%, gels exhibited a single discontinuous volume transition at 36-38 °C. However, for SDS concentration above 0.5 wt%, two discontinuous volume transitions at 36-40 and 70 °C were observed. Additionally, the replacement of BIS by the novel octafunctional crosslinker glyoxal bis(diallylacetal) (GLY) yielded an increase in the swelling ratio.     

Thermoreversible hydrogels. I. Synthesis and effect of a hydrophobic monomer on swelling behaviors of thermoreversible gels prepared by copolymerizing N-alkoxyalkylacrylamide with butyl acrylate

A series of copolymeric gels were prepared from N-alkoxyalkylacrylamide and n-butyl acrylate (BA) at various feed ratios. The effect of the content of BA in the copolymer on the gel behaviors is discussed. The respective crosslinked copolymer exhibits a gel transition behavior, collapsing and shrinking above gel transition temperature but swelling and reexpanding below gel transition temperature. By utilizing this character, these copolymeric gels could be used for drug release or drug delivery systems. The drug released from the copolymeric gels was plotted as M_t/M_∞ versus t, where M_t/M_∞ is the fraction of drug released at given time t. In this experiment, crystal violet and caffeine were chosen as model drugs. The deswelling-kinetics experiments with caffeine showed that a water pocket was formed within the gel matrix when the gel deswelled rapidly. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 1477–1484, 1997     

Synthesis and characterization of pH- and/or temperature-sensitive hydrogels

A series of pH-sensitive hydrogels that exhibit volume phase transition phenomena have been synthesized in aqueous solution and characterized with respect to their dynamic swelling behaviors. Positively charged hydrogels were prepared by copolymerizing varying ratios of N-isopropylacrylamide and NN′-dimethylaminopropylmethacrylamide. The hydrogels based on a temperature-sensitive hydrogel demonstrate a large change of equilibrium swelling in response to small variations of pH and/or temperature. These hydrogels exhibit different lower critical solution temperature (LCST) ranges depending on the environmental pH values. Below their LCST, they exhibit small and broad pH sensitivities normally observed in most hydrophilic polyelectrolyte gels, but above their LCST, they exhibit sharp pH dependent phase transition behaviors. The pH-dependent phase transition is strongly affected by temperature, while the temperature-dependent transition is, in turn, largely influenced by the pH. As the temperature is raised, the transitional degree of gel swelling change becomes sharper and larger, and the phase transition pH value shifts to a lower pH. It was also found that swelling is faster than deswelling for these cationic hydrogels, which suggests the existence of a water diffusion barrier during the deswelling. The swelling kinetics of initially dry and glassy gels were strongly dependent on both the pH value and temperature.     

Synthesis and characterization of biresponsive graft copolymer gels

Graft copolymer gels with different compositions were prepared by the radical polymerization of N-isopropylacrylamide (NIPAAm) and poly(2-vinylpyridine) (P2VP) macromonomers in dioxane with 1 mol% N,N′-methylenebisacrylamide (BIS) as the crosslinking agent. The graft copolymer gels were analyzed at different temperatures and pH values. They demonstrated the typical swelling behavior for poly(N-isopropylacrylamide) (PNIPAAm) gels with changing temperature. In addition to the temperature dependent measurements, the graft copolymer with a high P2VP content showed a pronounced swelling transition with changing pH value. By separating the temperature and the pH sensitive component, it was possible to obtain a gel which could be swelled independently in response to temperature and pH.     

Thermoreversible hydrogels. VII. Synthesis and swelling behavior of poly(N‐isopropylacrylamide‐co‐3‐methyl‐1‐vinylimidazolium iodide) hydrogels

A series of N‐isopropylacrylamide/3‐methyl‐1‐vinylimidazolium iodide (NIPAAm/MVI) copolymer gels were prepared from the various molar ratios of NIPAAm, cationic monomer MVI, and N,N′‐methylene bisacrylamide (NMBA) in this study. The influence of the amount of MVI in the copolymer gels on the swelling behaviors was investigated in various aqueous saline solutions. Results showed that the swelling ratios (SRs) of copolymer gels were significantly greater than those of NIPAAm homopolymer gels, and the higher the MVI content, the higher the volume phase transition temperature. The SRs for the NIPAAm/MVI copolymer gels decreased with an increase of the salt concentration. In various saline solutions, results showed that the effect of divalent ions on the SR was greater than that of monovalent ions for these hydrogels. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3242–3253, 1999     

Phase transition in swollen gels: 7. Effect of charge concentration on the temperature collapse of poly(N,N-diethylacrylamide) networks in water

The swelling and mechanical behaviour of gels of the copolymer of diethylacrylamide (DEAAm) with a small quantity of sodium methacrylate (mole fraction x_MNa = 0–0.067) swollen in water was investigated in the temperature range 1–80°C. For networks in the range x_MNa > 0.0095 phase transition was observed; both the critical transition temperature T_c,c and the extent of the collapse Δ_c increase with increasing x_MNa. The formation of associations in the collapsed state contributes to the overall extent of the transition; these structures give rise to stable turbid gels at elevated temperatures. Evidence for the formation of ‘associated’ structures is also supported by the observed independence of cloud temperature of the concentration of DEAAm, c, in the polymerization DEAAm-water mixture without the crosslinking agent in the range c = 0.5–80 vol%. While PDEAAm solutions are formed in the range c < 4.5–6 vol%, physical gels arise at higher concentrations.     

Synthesis,Characterization, and drug release study of acrylamide‐co‐itaconic acid based smart hydrogel

A new kind of pH and temperature responsive poly(acrylamide‐co‐itaconic acid) hydrogel was prepared by free radical polymerization using ammonium persulfate as initiator and different comonomer ratios. The hydrogels were characterized in terms of chemical composition, swelling‐deswelling behavior, morphology, crystallographic behavior, and drug release properties. All the hydrogels showed high swelling ability in aqueous solutions, the maximum being at pH 7. Swelling decreased on either side of pH 7 (i.e., both in acidic and alkaline region) and increased with increase in temperature. The hydrogel with 10 mol% itaconic acid (IA) absorbed maximum water among the copolymer gels. The cellular structures of the hydrogels were clearly revealed by microscopic analysis and SEM pictures. Swelling of the gels in water followed non‐Fickian type of diffusion principle. The hydrogel was proved to be a controlled release vehicle, for example in drug delivery by using its smart properties. The hydrogel with 10 mol% IA also absorbed maximum amount of drug (ascorbic acid) under study. Incorporation of drug in hydrogel matrix was established from XRD peak analysis. POLYM. ENG. SCI., 55:113–122, 2015. © 2014 Society of Plastics Engineers     

pH‐thermoreversible hydrogels. I. Synthesis and swelling behaviors of the (N‐isopropylacrylamide‐co‐acrylamide‐co‐2‐hydroxyethyl methacrylate) copolymeric hydrogels

A series of pH‐thermoreversible hydrogels that exhibited volume phase transition was synthesized by various molar ratios of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and 2‐hydroxyethyl methacrylate (HEMA). The influence of environmental conditions such as temperature and pH value on the swelling behavior of these copolymeric gels was investigated. Results showed that the hydrogels exhibited different equilibrium swelling ratios in different pH solutions. Amide groups could be hydrolyzed to form negatively charged carboxylate ion groups in their hydrophilic polymeric network in response to an external pH variation. The pH sensitivities of these gels also depended on the AAm content in the copolymeric gels; thus the greater the AAm content, the higher the pH sensitivity. These hydrogels, based on a temperature‐sensitive hydrogel, demonstrated a significant change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a dehydrated network response to small variations of temperature. pH‐thermoreversible hydrogels were used for a study of the release of a model drug, caffeine, with changes in temperature. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 221–231, 1999     

Thermosensitive networks based on high molecular weight polyoxyethylene and N-isopropylacrylamide

Summary γ- and UV-irradiation was successfully used for the preparation of mixed networks on the basis of high molecular weight polyoxyethylene (POE) and/or N-isopropylacrylamide and poly(N-isopropylacrylamide) (PNIPAAm). These gels preserve the swelling transition temperature of the pure PNIPAAm and shrink faster above this temperature due to the hydrophilic POE chains. It was found that in a collapsed state these gels retain alkaline organic salts from aqueous solutions. Received: 12 February 1999/Revised version: 18 May 1999/Accepted: 18 May 1999     

Biodegradable stimuli‐responsive hydrogels based on amphiphilic polyaspartamides with tertiary amine pendent groups

Novel thermo‐ and pH‐responsive hydrogels based on amphiphilic polyaspartamides possessing a lower critical solution temperature (LCST) and a volume‐phase transition were prepared and characterized. The polyaspartamide derivatives were synthesized from polysuccinimide, which is the polycondensate of L ‐aspartic acid monomer, through successive ring‐opening reactions using hydrophobic 2‐diisopropylaminoethylamine and hydrophilic ethanolamine. The amphiphilic copolymer was then crosslinked with hexamethylene diisocyanate to afford the corresponding gel. The LCST of the copolymer in an aqueous solution was varied by changing both the graft composition and pH of the medium. The crosslinked gels showed stimuli‐responsive behavior, with their degree of swelling and porous structure morphology changing with temperature and pH. In addition, hydrolytic degradation depending on the crosslinking density of the hydrogel was examined. Copyright © 2009 Society of Chemical Industry     

Thermoreversible hydrogels. XII. Effect of the polymerization conditions on the swelling behavior of the N‐isopropylacrylamide gel

The swelling behavior for the poly(N‐isopropylacrylamide) (NIPAAm) hydrogel prepared in various conditions such as various polymerization media, i.e., deionized water, acetone, and ethanol aqueous solution, and different polymerization temperatures were investigated in this work. The gels were also assessed for suitability in drug‐controlled release. The results indicated that the swelling behavior of the gel was dependent on the polymerization media and temperature, that is, the swelling ratios of gel were related to the pore size and the looser or denser structure of the gel. In addition, the pore size of the gel could be controlled by adjusting the surrounding temperature. Hence, the gel can be used to deliver drugs with different sizes. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 1604–1611, 2000     

Thermoreversible hydrogels. II. Effect of some factors on the swelling behavior of N,N-dimethylacrylamide and n-butoxymethyl acrylamide copolymeric gels

A series of thermoreversible hydrogels are prepared from the various molar ratios of N,N-dimethylacrylamide (DMA), n-butoxymethyl acrylamide (nBMA), and N,N′-methylenebisacrylamide (NMBA). The influences of the amount of DMA in the copolymeric gels, temperature, and polymerization media on the swelling behaviors in water are investigated. Results indicate that the higher the DMA content in the hydrogel systems the higher the swelling ratio and the gel transition temperature. The effects of the gel thickness on the swelling ratio for DMA/nBMA copolymeric gels indicate that the equilibrium swelling time and diffusion coefficient for the thinner gel (1.5 mm) from the dried state to the completely swollen state are obviously faster than are those for the thicker gels (2.0 and 3.5 mm). The effects of the different polymerization media on the swelling ratio for DMA/nBMA copolymeric gels also show that the larger the solvent molecular size and the poor miscibility of the monomer and solvent the higher the swelling ratio and the diffusion coefficient. The drug release in these copolymeric gel systems are also investigated. © 1997 John Wiley & Sons, Inc. J Appl Polm Sci 65:909–916, 1997     

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