Rapid Responsive Behaviors of the Dual Stimuli-Sensitive Poly(DEA-co-DMAEMA) Hydrogel via Comb-Type Grafted Polymeriziation

The dual-sensitive, comb-type grafted hydrogels were synthesized by grafting polymeric chains with freely mobile ends, which were composed of both N,N-diethylacrylamide (DEA) and (2-dimethylamino) ethyl methacrylate (DMAEMA), onto the backbone of crosslinked poly(DEA-co-DMAEMA) networks. The structure of the poly(DEA-co-DMAEMA) macromonomer was characterized by Nuclear Magnetic Resonance (¹H NMR) and Fourier transform infrared spectroscopy (FTIR). The effects of the feed components, temperature, and pH on the swelling behavior of the hydrogels were studied. With the increase of the poly(DEA-co-DMAEMA) macromonomer content, the thermo- and pH-sensitivity of the hydrogels improved. The G-PDD hydrogels exhibited improved thermo- and pH-sensitive characteristics, such as faster deswelling and reswelling rates and great oscillating deswelling/swelling behavior, and the level of improvement depended on the poly(DEA-co-DMAEMA) macromonomer content. The proposed dual thermo- and pH-sensitive, comb-type grafted poly(DEA-co-DMAEMA) hydrogel has various potential applications.     

Dual thermo- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors

Novel dual temperature- and pH-sensitive comb-type grafted poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AAc)) hydrogels were successfully prepared by grafting PNIPAM chains with freely mobile ends onto the backbone of a cross-linked P(NIPAM-co-AAc) network. The prepared comb-type grafted P(NIPAM-co-AAc) hydrogels exhibited a more rapid deswelling rate than normal-type P(NIPAM-co-AAc) hydrogels in ultrapure water in response to abrupt changes from 25 °C to 60 °C. The same was true in buffer solution with a pH jump from 7.4 to 2.0 at 25 °C. Unexpectedly, the comb-type grafted P(NIPAM-co-AAc) hydrogels showed abnormal shrinkage behaviors in a buffer solution when the temperature increased from 25 °C to 60 °C with a pH value fixed at 7.4 or 2.0. In a buffer solution of pH 7.4, when the environmental temperature jumped from 25 °C to 60 °C, the grafted comb-type hydrogels shrank slower than the normal-type hydrogels, while at pH 2.0, the gels shrank faster than the normal-type gels in the beginning, which was followed by a slower shrinking. Interestingly, the much quicker shrinkage of the comb-type grafted P(NIPAM-co-AAc) hydrogels was observed because of the cooperative thermo-/pH-responses when the simultaneous temperature and pH stimuli met from pH 7.4/25 °C to pH 2.0/60 °C. The results of this study provide valuable information regarding the development of dual stimuli-sensitive hydrogels with fast responsiveness.     

Temperature- and solvent-sensitive hydrogels based on N-isopropylacrylamide and N,N-dimethylacrylamide

Summary The swelling behaviour in water-dioxane mixtures of hydrogels containing N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMAM) is investigated as a function of dioxane content and temperature. The composition of the hydrogels, reported as the mol percentage of DMAM units, x, varies from 0 up to 100. It is found that the hydrogel containing only NIPAM units, GPNIPAM, deswells significantly in the water-rich region, while the hydrogel containing only DMAM units, GPDMAM, presents a pronounced deswelling in the dioxane-rich region. This deswelling becomes less significant with decreasing the DMAM content x, when using the hydrogels of the copolymers GP(NIPAM-co-DMAMx). This swelling behaviour of the hydrogels results from a combination of the lower critical solution temperature-type cononsolvency behaviour of poly(N-isopropylacrylamide) with the upper critical solution temperature-type cononsolvency behaviour of poly(N,N-dimethylacrylamide) in water-dioxane mixtures.     

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 of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(l-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and the release data suggested that both the pH and PNH content played important roles in the drug release behaviors of the hydrogels.     

Synthesis and Characterization of Temperature-Sensitive Poly(N-isopropylacryamide) Hydrogel with Comonomer and Semi-IPN material

A series of temperature and pH sensitive hydrogels were synthesized using N-isopropylacrylamide (NIPAAm) as main monomer, sodium alginate (SA) as semi-IPN material, ethyl acrylate (EA) and acrylic acid (AA) as comonomer, and N-maleyl chitosan (N-MACH) as cross-linker. The temperature and pH sensitive behavior, swelling/deswelling kinetics of the hydrogels were investigated. And the mechanism of the phase transition was summed up. Sodium alginate/Poly(N-isopropylacryamide) semi-interpenetrating polymer network (SA/PNIPAAm semi-IPN) hydrogels exhibited a lower critical solution temperature (LCST) at about 32 °C with no significant deviation from the conventional PNIPAAm hydrogels. Poly(N-isopropylacryamide-co-ethyl acrylate) (P(NIPAAm-co-EA)) hydrogels exhibited LCST at 29–31°C, increasing the amount of EA in the hydrogel gradually decreased the LCST. Poly(N-isopropylacryamide-co-acrylic acid) [P(NIPAAm-co-AA)] hydrogels exhibited LCST at 34–39°C, with decreasing NIPAAm/AA from 96/4 to 92/8 and 90/10, the LCST increased from 34°C to 37°C and 39°C. In the swelling/deswelling kinetics, all the dried hydrogels exhibited fast swelling/deswelling behavior, which might be attributed to macroporous structures of the hydrogels.     

Synthesis and properties of thermosensitive, crown ether incorporated poly(N-isopropylacrylamide) hydrogel

A crown ether derivative (4′-allyldibenzo-18-crown-6, CE) was covalently incorporated into the network of temperature sensitive poly(N-isopropylacrylamide) (PNIPA) hydrogels by copolymerization in a mixed solvent of water and tetrahydrofuran (H₂O/THF). The poly(N-isopropylacrylamide-co-4′-allyldibenzo-18-crown-6) (poly(NIPA-co-CE)) hydrogels exhibited dramatically faster deswelling rates than normal PNIPA hydrogels at a temperature (50 °C) above their lower critical solution temperatures. The effect of the solvent component ratio in the mixed solvent during the copolymerization on the swelling properties of the poly(NIPA-co-CE) hydrogel was investigated. The thermosensitive poly(NIPA-co-CE) hydrogels have potential applications in the extraction of cations and separation of chiral drugs.     

Rapid temperature/pH response of porous alginate-g-poly(N-isopropylacrylamide) hydrogels

To improve the swelling and deswelling rate, comb-type macroporous hydrogels were prepared. The temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) was grafted on the surface or bulk of the pH-responsive alginate. The larger surface area in pores and free chain mobility by comb-type graft copolymer reached its equilibrium swollen state within a minute. The swelling ratio of porous hydrogel in equilibrium state was over fifteen times greater than that of nonporous hydrogels. The increase of surface area by pores caused water molecules to transfer easily in and out of the matrix, resulting in a rapid deswelling. The degree of change in swelling ratio during deswelling might be affected by the phase transition behavior of PNIPAAm attached on only the surface of the pore rather than PNIPAAm grafted into mainchain of alginate. Surface-grafted alginate/PNIPAAm gels had a suitable mechanical strength without collapsing during the repeatable shrinkage and expansion due to swelling and deswelling, whereas bulk-grafted gels easily collapsed.     

A study of hydrogel thermal-dynamics using Fourier transform infrared spectrometer

A rapid and reliable method was presented for studying hydrogel dynamics/kinetics. Two temperature-sensitive hydrogels, poly-N-isopropylacrylamide (poly(NIPAAm)) and the copolymer of N,N-diethylacrylamide and sodium methacrylate (molar ratio=97:3, poly(NDEAAm-co-MAA)) were synthesized. The thermal-behaviors of the gels were studied through the absorbance intensities of both swollen water and gel frame components, and the peak positions of amide band along heating/cooling pathways under dynamic Fourier transform infrared (FTIR) probing. The results showed that the lower critical solution temperature (LCST) of poly(NIPAAm) is about 33-35 °C, which is consistent with reported value of ∼34 °C. Compared to poly(NIPAAm), poly(NDEAAm-co-MAA) has relatively continuous volume phase transition, starting at ∼35 °C and a better thermal-reversibility with similar swelling and deswelling profiles over a larger temperature range (10-80 °C for poly(NDEAAm-co-MAA) vs. 10-33 °C for poly(NIPAAm)). The H-bonding water along phase transition was also studied, showing a less reversibility of poly(NIPAAm) compared to poly(NDEAAm-co-MAA). In addition, FTIR spectrometer was also used to study the volume changes of poly(NDEAAm-co-MAA) under variations in environmental salinity.     

Fast responsive and strong swelling hydrogels based on N‐isopropylacrylamide with sodium acrylate

Poly(N‐isopropylacrylamide‐co‐sodium acrylate) gels with N,N‐methylene bisacrylamde (BIS) as crosslinker were prepared by free radical polymerization method at the temperature of 35°C, which was just around the lower critical solution temperature (LSCT) of the hydrogels. The gels synthesized at 35°C demonstrated strong swellability and fast responseability when compared with the gels synthesized at the temperature of 0 and 18°C (below the LCST) and 50 and 80°C (above the LSCT). The response rate and swelling behavior of poly(N‐isopropylacrylamide‐co‐sodium acrylate) gels was investigated and characterized by the temperature‐dependent swelling ratio and swelling and deswelling kinetics. The swelling behavior of the gels indicated that the synthesis temperature was the main factor when the swellability concerned and also had effect on the responseability of the resulting hydrogels. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

Synthesis and characterization of fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels

BACKGROUND: A considerable amount of research has been focused on smart hydrogels that can respond to external environmental stimuli, especially temperature and pH. In this study, fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels were prepared by free radical copolymerization in aqueous solution using poly(ethylene glycol) (PEG) as a pore‐forming agent. RESULTS: Swelling studies showed that the hydrogels produced had both temperature and pH sensitivity. The deswelling kinetics at high temperature demonstrated that the shrinking rates were influenced by the addition of the pore‐forming agent and the amount of acrylic acid in the initial total monomers. The deswelling curves in low‐buffer solutions had two stages. Pulsatile swelling studies indicated that the PEG‐modified hydrogels were superior to the normal ones. These different swelling properties were further confirmed by the results of scanning electron microscopy. CONCLUSION: Such fast responsive thermo‐ and pH‐sensitive hydrogels are expected to be useful in biomedical fields for stimuli‐responsive drug delivery systems. Copyright © 2008 Society of Chemical Industry     

Synthesis of rapid responsive gels comprising hydrophilic backbone and poly(N-isopropylacrylamide) graft chains by RAFT polymerization and end-linking processes

A thermosensitive poly(N-isopropylacrylamide) (PNIPAM) grafted gel, which comprises hydrophilic backbone and freely mobile PNIPAM graft chains, was synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization and end-linking processes. Functional PNIPAM bearing dithiobenzoate end group (-C(S)S-R) was prepared first, and then it was reacted with divinyl compounds to obtain gel. In order to adjust the composition of the gels, two divinyl compounds, N,N-methylenebisacrylamide (BIS) and poly(ethylene glycol) diacrylate (PEGDAC), were used. The cross-linking polymerization mechanism was proposed. The swelling and deswelling kinetics of the hydrogels were measured. The gels exhibit rapid deswelling kinetics. At the same time, they show rapid swelling kinetics within 30 min, whereas a conventional PNIPAM-co-PEG-co-BIS gel with the same feed composition requires more than 10 h to reach swelling equilibrium.     

Synthesis of poly(N-isopropylacrylamide) copolymer containing anhydride and imide comonomers - A theoretical study on reversal of LCST

The stimuli sensitive copolymer NIPAM-co-MI was prepared by copolymerizing NIPAM (N-isopropylacrylamide) with varying concentrations of maleimide (MI). The copolymer showed the same ratio of the monomeric components as that of the initial monomer feed ratio, with the two components arranged in the chain in a purely random sequence. Interestingly, the lower critical solution temperature (LCST) of NIPAM-co-MI was found to decrease with increase in MI loading in the copolymer. This behavior was in drastic contrast to the LCST behavior of a similar copolymer NIPAM-co-MA of NIPAM and maleic anhydride (MA) where the LCST showed an increase with increase in the MA concentration. A theoretical interpretation of the contrasting LCST behavior of both NIPAM-co-MI and NIPAM-co-MA was obtained by quantum mechanical (QM) modeling on small structural units of the polymers as well as molecular dynamic (MD) simulations at LCST and above the LCST on 50-unit oligomer model of the polymers. The QM models showed that the MI based polymer is more inclined towards bend structure, higher hydration, and higher intramolecular hydrogen bond formation between its monomer units when compared to those of the MA based polymer. The results of the large scale MD simulation was in complete support of the QM results as it showed the formation of a more folded and highly hydrated NIPAM-co-MI than NIPAM-co-MA.     

Rapid swelling and deswelling of thermoreversible hydrophobically modified poly(N-isopropylacrylamide) hydrogels prepared by freezing polymerisation

Rapid response thermally sensitive hydrophobically modified poly(N-isopropylacrylamide) hydrogels have been synthesised successfully using a two-step polymerisation method, the initial polymerisation being carried out at 20 °C, followed by polymerisation at −28 °C for 24 h. The results show that the swelling/deswelling rates of poly[N-isopropylacrylamide-co-(di-n-propylacrylamide)] P(NIPA-co-DPAM) hydrogels prepared by two-step polymerisation are much faster than for the same type of hydrogels prepared via conventional methods (30 °C for 24 h), i.e. the time for the former xerogel to absorb 70 and 90 wt% is just 30 and 240 min, respectively, compared to the latter xerogel which takes 1600 and 2500 min to absorb the same amounts of water. During deswelling (shrinking), the hydrogel loses 95 wt% water in 1 min, compared to a timescale for the corresponding cross-linked copolymers prepared by conventional methods of about 5 h for 50 wt% water loss. Scanning electron microscopy, and flotation experiments together with swelling ratio studies reveal that the polymeric network of the former hydrogel is characterised by an open structure with more pores and higher swelling ratio but lower mechanical strength compared to the latter hydrogels. Such rapid response hydrogels have potential applications in separation and drug release technologies for example.     

Preparation and microstructural analysis of poly(ethylene oxide) comb‐type grafted poly(N‐isopropyl acrylamide) hydrogels crosslinked by poly(ϵ‐caprolactone)

Poly(N‐isopropyl acrylamide) (PNIPAAm)‐graft‐poly(ethylene oxide) (PEO) hydrogels crosslinked by poly(?‐caprolactone) diacrylate were prepared, and their microstructures were investigated. The swelling/deswelling kinetics and compression strength were measured. The relationship between the structure and properties of hydrogel are discussed. It was found that the PEO comb‐type grafted structure reduced the thermosensitivity and increased the compression strength. The addition of poly(?‐caprolactone) (PCL) accelerated the deswelling rate of the hydrogels. Meanwhile, the entanglement of PCL chains restrained the further swelling of the network of gels. The PCL crosslinking agent and PEO comb‐type grafted structure made the behavior of the hydrogels deviate from the rubber elasticity equations. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

A novel temperature and pH dual‐responsive hybrid hydrogel with polyhedral oligomeric silsesquioxane as crosslinker: synthesis,characterization and drug release properties

Octavinyl polyhedral oligomeric silsesquioxane (OVPS) is used as the crosslinker instead of N,N′‐methylenebisacrylamide (BIS) to copolymerize with 2‐(dimethylamino)ethyl methacrylate (DMAEMA) or DMAEMA and N‐isopropylacrylamide (NIPAM) to prepare hybrid hydrogels: P(OVPS‐co‐DMAEMA) and P(OVPS‐co‐DMAEMA‐co‐NIPAM). The prepared hydrogels are transparent and show dual response to temperature and pH. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, dynamic mechanical analysis and tensile tests. Their mechanical properties, swelling ratio, deswelling and reswelling behaviors as well as drug release properties were investigated. The results indicate that OVPS can be incorporated into polymer networks in proportion to feed ratios. The P(OVPS‐co‐DMAEMA) hydrogel exhibits more homogeneous interior structure, higher swelling ratio and faster response than the conventional hydrogel prepared with BIS. Moreover, the incorporation of OVPS enhances the compression and tensile properties of the hydrogels. The feed ratios of OVPS and NIPAM have a great effect on volume phase transition temperature, thermal sensitivity, swelling behavior, mechanical properties and drug release properties of the hybrid hydrogels. The prepared dual‐responsive OVPS‐containing hydrogels are expected to be used as biomedical materials in drug release and tissue engineering. © 2014 Society of Chemical Industry     

Ionization‐induced ultrarapid response behavior of fibrous and porous electrospun hydrogels containing carboxyl groups

Fibrous porous membranes composed of poly(N‐isopropylacrylamide‐co‐acrylic acid) and poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) were prepared by electrospinning. The membranes behaved like hydrogels in water after being crosslinked at elevated temperatures. Investigations of the swelling and deswelling behavior indicated that the response rates significantly increased after the carboxyl and/or anhydride groups in the hydrogel membranes were ionized or neutralized with NaOH. It took them less than 60 s to reach equilibrium swelling and about 90 s to reach equilibrium deswelling. The response rates were much higher than those of the parent un‐ionized membranes; this indicated that ionization played an important role in the ultrarapid response behavior. The response rate was also higher than that of most hydrogel materials previously reported and was even comparable to superporous hydrogels with high moisture contents. The mechanism of the ultrarapid response behavior of the ionized membranes was qualitatively analyzed. We believe that the fine fiber diameter, high porosity, and improved wettability with water contributed to the ultrarapid response behavior. This study presents a new and facile method for improving the response rate of hydrogel materials made by electrospinning. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Dual thermo-responsive and ion-recognizable monodisperse microspheres

A novel type of dual stimuli-responsive microspheres that simultaneously exhibit ion-recognition property based on the supramolecular host-guest complexation of crown ether receptors (benzo-18-crown-6-acrylamide) (BCAm) with specific ions and thermo-sensitivity based on the phase transition of poly(N-isopropylacrylamide) (PNIPAM) is fabricated in this study. The prepared poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (P(NIPAM-co-BCAm)) microspheres are characterized by FT-IR spectroscopy, UV-vis absorption spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). SEM images and DLS data show that the synthesized microspheres exhibit nearly perfect spherical shape and high monodispersity. Moreover, according to the DLS results, P(NIPAM-co-BCAm) microspheres exhibit satisfactory thermo-responsive behavior and ion-recognition property. In K⁺ solutions, due to the formation of crown ether/K⁺ complexes, the LCST of P(NIPAM-co-BCAm) microspheres shifts to a higher temperature and the colloidal stability is increased. The P(NIPAM-co-BCAm) microspheres undergo a volume change from shrunken state to swollen network isothermally at a certain temperature by the addition of metal ions. Due to dual thermo-responsive and ion-recognition behaviors, this kind of microspheres would serve as promising candidates for sensors, controlled drug delivery systems and possibly new biomaterials.     

Preparation of a novel pH-sensitive hydrogel based on acrylic acid and polyhedral oligomeric silsesquioxane for controlled drug release of theophylline

Hydrogels based on pH-sensitive polymers are of great interest as potential biomaterials for the controlled delivery of drug molecules. In this study, a novel pH-sensitive copolymer hydrogel based on acrylic acid (AA) monomer by free-radical solution polymerization were synthesized with organic–inorganic cross-linking agent of octavinyl polyhedral oligomeric silsesquioxane (OVPOSS). And its properties were compared with conventional hydrogels using N,N′-methylenebisacrylamide (MBA) as cross-linking agent. The copolymers were characterized by Fourier transform infrared spectra and differential scanning calorimetry. The morphology after swelling was presented by scanning electron microscopy. Swelling behaviors in different pH and potential applications in controlled drug delivery of the hydrogels were also examined. The results showed that both hydrogels were pH sensitive. However, as the addition of OVPOSS limited the movement of the molecular chain segment, the swelling ratio and the drug-release rate of theophylline in SGF decreased obviously when using OVPOSS as cross-linking agent, comparing with P(MBA-co-AA) hydrogels. The results in this study suggested that P(OVPOSS-co-AA) could serve as potential candidate for theophylline drug delivery.