On the water swelling behaviour of poly(N-isopropylacrylamide) [P(N-iPAAm)], poly(methacrylic acid) [P(MAA)], their random copolymers and sequential interpenetrating polymer networks (IPNs)

Thermo- and pH-responsive stimuli hydrogels based on N-isopropylacrylamide (N-iPAAm) and methacrylic acid (MAA) have been synthesized and their swelling behaviour studied as a function of composition, pH and temperature. Copolymers varying in composition have been obtained by copolymerizing these two monomers and interpenetrating polymer networks (IPNs) of P(MAA) and P(N-iPAAm) by the sequential method. Temperature and pH have been changed in the ranges from 25 to 40 °C and from 2 to 9, respectively. The swelling behaviour of the hydrogels depends on the nature of the polymer and the environmental conditions, namely pH and temperature. Copolymer gels under basic conditions exhibit higher degree of swelling than the homopolymer ones. The disruption of the complexes dominates the kinetic swelling of MAA enriched gels under basic conditions. The hydrogen bond formation between carboxyl and amide groups has been made clear through the dynamic swelling behaviour of copolymers under acidic conditions. IPNs reduce their ability to swell in water with increasing P(N-iPAAm) content because of the formation of hydrophobic interpolymer complexes through hydrogen bonding. Lower critical solution temperature occurs only in the enriched N-iPAAm copolymers under acidic conditions when the MAA carboxyl groups are unionized.     

Influence of the swelling history on the swelling kinetics of stimuli-responsive poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels

The influence of the swelling history on the swelling behavior of poly[(N-isopropylacrylamide)-co-(methacrylic acid)] P[(N-iPAAm)-co-(MAA)] random copolymers hydrogels synthesized by free radical polymerization in solution of N-iPAAm and MAA comonomers crosslinked with tetraethylene glycol dimethyl acrylate (TEGDMA) has been studied. The swelling behavior under pH 7 at 18, 29, 39 and 49 °C of this series of copolymers, previously soaked either at pH 2 or 7 has been investigated. The swelling kinetics of these two series of samples displays different behavior as function of the composition and temperature. However, the equilibrium swelling values only show slight dependences on the previous soaking pH and temperature. When samples are soaked at pH 7, then the swelling at pH 7 follows a first order kinetics, irrespective of the copolymer composition or the temperature at which the experiment has been carried out. In this case, the swelling process is very fast and depends only slightly on temperature. The first order rate constant increases with the MAA content in the hydrogel. Furthermore, the swelling rate of copolymer hydrogels soaked at pH 2, show strong dependence on composition and temperature. They follow an autocatalytic swelling kinetics due to the disruption of hydrogen bond arrangements. An initial slow water uptake is followed by an acceleration process, in which water molecules inside the gel help the next water molecules to come in. Two rate constants, a first-order rate constant and an autocatalytic one have been obtained from the kinetics analysis. They have revealed different temperature dependence which may be due to a balance between hydrophobic and hydrogen bond interactions. The temperature dependence of the swelling kinetics is stronger and more complex for copolymers treated under pH 2 than for copolymers soaked under pH 7.     

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.     

pH-Controlled association of PEG-containing terpolymers of N-isopropylacrylamide and 1-vinylimidazole

Temperature- and pH-controlled association of terpolymers of N-isopropylacrylamide (NIPA) with 1-vinylimidazole (VI) and polyethylene glycol (PEG) has been investigated by light scattering and atomic force microscopy (AFM) in situ. The polymers contained 0-15 mol% VI and 0-2 mol% PEG. The phase transition temperatures (T_p) have been in the range of 32-45 °C and exhibited significant dependence on the pH of solution in the pH range between 5 and 8. The T_p of the polymers increased with increasing VI content and with decreasing pH, confirming major effect of VI ionization status on T_p. The presence of PEG grafts in the polymer structure had augmenting effect on the magnitude of pH-responsiveness and on the pH-independent colloidal stability of the polymer particles formed above T_p. Incorporation of VI into the polymer structure had similar, but pH-dependent effect on colloidal stabilization of the polymer particles. The size of the particles formed after the phase transition is driven by the association of the collapsed NIPA segments in the globule conformation and it decreased with decreasing pH. The phase transition temperature of the polymers could be adjusted to increase from temperatures below, to temperatures above body temperature upon decreasing pH from 7 to 6, suggesting that such polymers could provide a material platform for a variety of biomedical applications. AFM analysis in situ showed a fully reversible formation of particles in the solutions of the polymers above their T_p.     

Copolymer hydrogels based on N-isopropylacrylamide and itaconic acid

In this study, the swelling behaviour of copolymer hydrogels of N-isopropylacrylamide (NIPAM) and itaconic acid (IA) in response to temperature and pH value of the external media was studied. The equilibrium degree of swelling for PNIPAM and PNIPAM/IA copolymers was greater at 25 °C than at 37 °C. The degree of swelling was low at low pH values. As the degree of ionization increased above the nominal pK_a values of IA, the increased hydrophilicity resulted in larger degrees of swelling. At 37 °C, the PNIPAM hydrogel and some copolymers show anomalous swelling behaviour, i.e. the overshooting effect, in buffered solutions of certain pH values. A swelling-deswelling study showed that the deswelling process of the hydrogels was faster then the swelling process. According to dynamic swelling studies, the diffusion exponent and the diffusion coefficient both increase with increasing content of IA.     

Poly(N-isopropylacrylamide) hydrogels with improved shrinking kinetics by RAFT polymerization

Functional poly(N-isopropylacrylamide) (PNIPAM) hydrogels were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAM) in the presence of N,N-methylenebisacylamide (BIS) as a cross-linker and 4-cyanopentanoic acid dithiobenzoate as chain transfer reagent (CTA). The swelling behaviors were investigated and the hydrogels by RAFT polymerization (RAFT gels) showed accelerated shrinking kinetics and higher swelling ratio comparing with conventional hydrogel (CG). It could be attributed to the presence of dangling chains mainly caused by CTA, which could retard the crosslinking reaction rate greatly. Another CTA, 3-(trithiocarbonyl) propanoic acid, was adopted to further investigate the effect of CTA. It showed the similar effect except the different accelerated degree to the shrinking kinetics. Furthermore, the living character of the RAFT process was used to polymerize a new batch of monomer (NIPAM) from functional RAFT gels to introduce grafted structure. The PNIPAM-g-PNIPAM hydrogels indicted further accelerated shrinking kinetics than functional backbone hydrogels.     

Swelling and mechanical behavior of poly(N-isopropylacrylamide)/Na-montmorillonite layered silicates composite gels

Clay-polymer hydrogel composites have been synthesized based on poly(N-isopropylacrylamide) (PNIPAM) gels containing 0.25-4 wt% of the expandable smectic clay Na-montmorillonite layered silicates (Na-MLS). The morphology of the composite gels has been studied using a polarized optical microscope. The size of Na-MLS aggregates increases with Na-MLS concentration. The swelling ratio of the Na-MLS/PNIPAM composite in water is increased at the low Na-MLS concentration but decreases as the concentration increases. Correspondingly, the shear modulus of the gel is found to exhibit a distinct minimum against clay concentration. For Na-MLS concentrations ranging from 2.0 to 3.2 wt%, the composite gels have larger swelling ratio and stronger mechanical strength than those for a pure PNIPAM. The presence of Na-MLS does not affect the value of the lower critical solution temperature (LCST) of the PNIPAM. However, the gel volume change at the LCST is first increased and then decreased upon the increase of the Na-MLS. No pH induced phase transition is observed for the Na-MLS/PNIPAM composites. The experimental results can be explained by considering that Na-MLS is physically entrapped inside rather than chemically bonded into the gel.     

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.     

Direct synthesis of syndiotactic-rich poly(N-isopropylacrylamide) via radical polymerization of hydrogen-bond-complexed monomer

Radical polymerization of N-isopropylacrylamide (NIPAAm) in toluene was investigated in the presence of hexamethylphosphoramide (HMPA). We succeeded in directly preparing syndiotactic-rich poly(NIPAAm), the syndiotacticity of which (r=70%) is the highest among those of radically-prepared poly(NIPAAm)s so far reported, by lowering polymerization temperature to −60 °C in the presence of a two-fold amount of HMPA. The NMR analysis revealed that the induced syndiotactic-specificity was ascribed to 1:1 complex formation between NIPAAm and HMPA. Furthermore, thermodynamic analysis described that the induced syndiotactic-specificity was enthalpically achieved.     

Heterotactic poly(N-isopropylacrylamide) prepared via radical polymerization in the presence of fluorinated alcohols

Radical polymerization of N-isopropylacrylamide in toluene at −40 °C in the presence of fourfold amounts of fluorinated alcohols was investigated. The ¹³C NMR analysis of the obtained polymers suggested that the addition of fluorinated alcohols induced heterotactic specificity in radical polymerization of NIPAAm, although syndiotactic poly(NIPAAm)s were obtained by adding alkyl alcohols as we have previously reported. To the best of our knowledge, this is the first synthesis of heterotactic poly(NIPAAm).     

Super porous organic-inorganic poly(N-isopropylacrylamide)-based hydrogel with a very fast temperature response

Porous organic-inorganic (O-I) hydrogels showing a very fast temperature response, including very fast reswelling were prepared: only 6 s are needed for 72% deswelling (gel collapse) as well as for 72% reswelling. Both deswelling and reswelling are practically complete in 14 s. The gels were prepared from N-isopropylacrylamide (NIPA), N,N′-methylenebisacrylamide (BAA) and tetramethoxysilane (TMOS) by simultaneous radical polymerization and hydrolytic polycondensation of TMOS. The syntheses were carried out at temperatures below the lower critical solution temperature (LCST) of poly(NIPA) in two steps: during the first stage the temperature was held at T = +15 °C and during the second the temperature was lowered below the freezing point of the reaction mixture, T = −18 °C. The ice crystals, which grew during the second stage, served as the pore-forming agent. The best samples were obtained if the second stage was started shortly before the gel point of the reaction mixture. The introduction of the inorganic phase (silica) is necessary for the ability of fast reswelling and also results in a strong improvement of the hydrogels' mechanical properties, while the maximum swelling degree remains nearly unaffected.     

Temperature dependence of density of polymer gels: Effects of ionizable groups in copoly(N-isopropylacrylamide/acrylic acid or sodium acrylate)-water systems

Effects of ionizable groups in hydrogels of copolymer networks on the volumetric contraction-expansion process were investigated. Polymer networks used were: copoly[N-isopropylacrylamide (NIPA)(1 − x)/acrylic acid (HAc) or sodium acrylate (NaAc)(x)] with mole fraction of minor component (x) assuming 0.0114 and 0.0457. From the temperature (T) dependence of total volume of gels, densities of the polymer and solvent (water) components, and stoichiometry, we evaluated (1) the volume of gels occupied by a single mean polymeric residue and associated water molecules (expressed in units of nm³), mean v_sp(gel), and (2) number of water molecules per single mean polymeric residue, mean N_s(gel), from near 273 K to 323 K. These quantities (1) and (2) listed above showed how acid and salt forms affect differently on volumetric changes of gels over 50 K. We developed an approach to evaluate volumetric changes of gels solely caused by a single polymeric residue of a minor component (x < 0.05) plus associated water by applying thermodynamic first-order perturbation theory. They are specific v_sp(gel)(T) for a single HAc or NaAc polymeric residue plus associated water and the corresponding specific N_s(gel)(T). Specific v_sp(gel)(HAc or NaAc)(T) and the corresponding specific N_s(gel(T)) revealed specific characteristics in thermal behavior near their respective transition temperatures from the swollen to shrunken states. We found these thermal changes shown at the nano-scale match very well with specific changes in the molality(T) of both ionizable groups. In fact, these are directly triggered by varying contents of water in gels. Based on the understanding of dissociative equilibrium attained by ionizable groups, we successfully replaced Na⁺ in hydrogels of copoly[NIPA(1 − x)/NaAc(x)] (x = 0.0457) by hydrogen ions. Absence of Na⁺ in treated hydrogels was experimentally verified by ²³Na NMR and Na atomic absorption flame photometry. Discontinuity in the volumetric contraction-expansion process from the swollen to shrunken states and vice versa was not observed in contradiction to the previous reports [Hirotsu S, Hirokawa Y, Tanaka T. J Chem Phys 1987;87:1392-5. Matsuo SE, Tanaka T. J Chem Phys 1988;89:1695-703.] obtained by the conventional swelling experiments.     

Effect of hydrophobic polystyrene microphases on temperature-responsive behavior of poly(N-isopropylacrylamide) hydrogels

Reversible addition-fragmentation chain transfer polymerization was employed to prepare the crosslinked poly(N-isopropylacrylamide)-graft-polystyrene networks (PNIPAAm-g-PS). Due to the immiscibility of PNIPAAm with PS, the crosslinked PNIPAAm-g-PS copolymers displayed the microphase-separated morphology. While the PNIPAAm-g-PS copolymer networks were subjected to the swelling experiments, it is found that the PS block-containing PNIPAAm hydrogels significantly exhibited faster response to the external temperature changes according to swelling, deswelling, and reswelling experiments than the conventional PNIPAAm hydrogels. The improved thermo-responsive properties of hydrogels have been interpreted on the basis of the formation of the specific microphase-separated morphology in the hydrogels, i.e., the PS blocks pendent from the crosslinked PNIPAAm networks were self-assembled into the highly hydrophobic nanodomains, which behave as the microporogens and thus promote the contact of PNIPAAm chains and water. The self-organized morphology in the hydrogels was further confirmed by photon correlation spectroscopy (PCS). The PCS shows that the linear model block copolymers of PNIPAAm-g-PS networks were self-organized into micelle structures, i.e., the PS domains constitute the hydrophobic nanodomains in PNIPAAm-g-PS networks.     

Hydrogen-bond-assisted isotactic-specific radical polymerization of N-isopropylacrylamide with pyridine N-oxide

Radical polymerization of N-isopropylacrylamide (NIPAAm) in CHCl₃ at low temperatures in the presence of pyridine N-oxide (PNO) was investigated. An isotactic poly(NIPAAm) with meso diad content of 61% was successfully prepared at −60 °C in the presence of a two-fold amount of PNO. Thermodynamic analysis suggested that the isotactic-specificity was entropically induced, probably due to conformational fixation near the propagating chain-end through coordination by PNO.     

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.     

Photo cross-linkable poly(N-isopropylacrylamide) copolymers III: micro-fabricated temperature responsive hydrogels

Micro-fabricated temperature responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels were produced by photolithographic patterning of photo cross-linkable polymers. These polymers were synthesized by copolymerization of N-isopropylacrylamide (NIPAAm) and 2-(dimethyl maleimido)-N-ethyl-acrylamide (DMIAAm). The patterning process of polymers with 9.2 mol% DMIAAm and film thickness below 5 μm in the dry state was able to depict a lateral resolution of 4 μm with insignificant shape change. In order to increase the adhesion of the swollen hydrogels, and thus, the resolution of a particular pattern, a special adhesion promoter based on a monochlorosilane anchor group and a chromophore head group was synthesized. If a silicon wafer surface was pretreated with the adhesion promoter, the structures were stable and well adhered even at lower cross-linking densities. The hydrogels are suitable as working substances for micro-actuators because of their thermally induced volume changes. The swelling ratio of the pattern at low temperatures increased with a decreased cross-linking density. As expected from the chemical composition of the gels, the phase transition temperature (T_c) decreased with increasing DMIAAm content. The swelling of microstructures in water in comparison to macroscopic objects occured significantly faster. This behavior was attributed to the small gel dimension but it was even more pronounced because of the sponge-like nanostructure of the hydrogels characterized by high-resolution field emission scanning electron microscopy. Suitable applications of these hydrogels are adjusting limbs in fluid micro-systems such as micro-pumps and micro-valves.     

Photosensitive copolymer of N-isopropylacrylamide and methacryloyl derivative of spyrobenzopyran

The copolymer of N-isopropylacrylamide (NIPAM) and methacryloyl derivative of spirobenzopyran (MSBP) with a molecular weight of 21?000 g/mol and the average molar MSBP content of 1.9% was prepared by free radical polymerization. The copolymer displayed its phase transition in water in the temperature range of 30-50 °C. UV irradiation of its aqueous solution caused photoinduced transformation of MSBP units into their coloured merocyanine forms, while the cloud point of the irradiated copolymer shifted by ca. 10 °C to lower temperatures. During a long-term exposure to daylight (20 days) the copolymer gradually elapsed to its colourless spiropyran form, the process being ca. 100-times slower than that for monomeric MSBP. Due to the slow reverse isomerization of its merocyanine form and low solubility in water at room temperature the UV irradiated copolymer could be quantitatively separated from aqueous solution by centrifugation.     

Synthesis and characterization of pH- and temperature-sensitive hydrogel of N-isopropylacrylamide/cyclodextrin based copolymer

A reactive β-Cyclodextrin (β-CD) based monomer carrying vinyl carboxylic acid functional groups was synthesized via reaction of β-CD with maleic anhydride (MAH) in N,N-dimethylformamide (DMF) at 80 °C. By copolymerization of the monomer with N-isopropylacrylamide (NIPA), a novel hydrogel, poly(NIPA-co-MAH-β-CD) with pH and temperature sensitivities plus molecular inclusion function, was obtained using free radical polymerization in aqueous solution. The hydrogel's composition was determined by element analysis and infrared spectroscopy. Equilibrium swelling ratio (ESR) of hydrogels was tested under different environment of pH, temperature and ionic strength. The results indicated that ESR of hydrogels presents marked variations following the change of experimental conditions used.     

Poly(ethylene oxide)-grafted poly(N-isopropylacrylamide) networks: Preparation, characterization and rapid deswelling and reswelling behavior of hydrogels

Poly(ethylene oxide)-grafted poly(N-isopropylacrylamide) networks (PNIPAAm-g-PEO) were prepared via the reversible addition-fragmentation chain transfer polymerization (RAFT) of N-isopropylacrylamide with trithiocarbonate-terminated poly(ethylene oxide) and N,N′-methylenebisacrylamide as the chain transfer agent and the crosslinking agent, respectively. It was found that the PNIPAAm-g-PEO copolymer networks were microphase-separated and that PEO microdomains were dispersed in the PNIPAAm matrix. The hydrogel behavior of the PNIPAAm-g-PEO networks was investigated using swelling, deswelling and reswelling tests. The PNIPAAm-g-PEO hydrogels displayed faster responses to external temperature changes than did the control PNIPAAm hydrogel.     

Thermosensitive poly(N-isopropylacrylamide) nanocapsules with controlled permeability

In this paper, novel thermosensitive poly(N-isopropylacrylamide) (PNIPAM) nanocapsules with temperature-tunable diameter and permeability are reported. Firstly, the core-shell composite microparticles were synthesized by precipitation polymerization with isothiocyanate fluorescein (FITC) entrapped SiO₂ as core and cross-linked PNIPAM as shell. Then, the SiO₂ core was etched by hydrofluoric acid at certain condition and the pre-trapped FITC molecules remained within the inner cavity. The FITC release profile and TEM studies clearly indicate that the release behavior of FITC could be controlled effectively by the external temperature. Above the LCST of PNIPAM (32 °C), the dehydrated PNIPAM shell inhibited the release of FITC from the internal cavity while below its LCST, the fluorophore could permeate the swollen shell easily.