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.     

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.     

Fabrication and characterization of microgel-impregnated, thermosensitive PNIPAAm hydrogels

Poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate (PNIPAAm/PEG-DA) microgels were used as an additive during the polymerization and/or crosslinking of PNIPAAm hydrogels to improve their thermosensitive properties. The influence of this additive on the property of resulting PNIPAAm hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that microgel impregnated PNIPAAm hydrogels have tighter and constrained porous network structures, although large cavities of 30-40 μm in diameter, occupied by the microgels were sporadically distributed in this constrained network. Differential scanning calorimetry (DSC) studies did not show apparent difference in lower critical solution temperature (LCST) between normal and microgel-impregnated PNIPAAm hydrogels. The incorporating of PNIPAAm/PEG-DA microgels, however, significantly improved mechanical properties of modified hydrogels when comparing with a normal PNIPAAm hydrogel, although the tendency was not strictly proportional to the microgel amount. Based on the temperature-induced swelling ratio data as well as response kinetics, microgel-impregnated hydrogels exhibited improved thermosensitive characteristics in terms of higher equilibrium swelling ratio as well as faster response rates and the level of improvement depended on the amount of microgel impregnated.     

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.     

Thermally responsive poly(N-isopropylacrylamide) monolayer on gold: synthesis, surface characterization, and protein interaction/adsorption studies

This report describes a novel method for preparing a thermally responsive poly(N-isopropylacrylamide) (PNiPAM) monolayer on a gold surface, and demonstrates the function of this monolayer in aqueous media. Thiol (-SH) terminated PNiPAM was synthesized by UV polymerization followed by hydrolysis, and a monolayer of this polymer (2.84±0.2 nm) was prepared on a gold substrate by simply dipping a precleaned gold plate into an aqueous solution of the PNiPAM. Cyclic voltametry and atomic force microscopy studies showed that the gold surface was well covered by the PNiPAM chains, and X-ray photoelectron spectroscopic data showed that this monolayer was chemisorbed on the gold surface. Studies of the water contact angle, protein interaction, and protein adsorption on the PNiPAM monolayer demonstrated that this monolayer shows a temperature dependence of the interfacial properties in aqueous media.     

Synthesis of graft polyacrylamide with responsive self-assembling properties in aqueous media

Graft copolymers with water-soluble backbones were prepared using two different routes: grafting onto and grafting through techniques. The corresponding syntheses, leading to ionic or non-ionic copolymers, are described here in detail and exemplified with various primary structures obtained by changing the chemical nature of the side chains or the grafting ratio. Depending on the polyelectrolyte or neutral character of water-soluble backbones, viscosity-concentration dependences were determined at room temperature in dilute and semi-dilute regimes. Upon heating, PNIPA grafts dehydrate and self-aggregate into hydrophobic microdomains which promote the formation of a physical network above 36 °C. The main features of the thermoassociating properties of the copolymers in aqueous solutions are described using different experimental approaches: rheology, calorimetry, NMR spectroscopy and neutron scattering.     

Effect of the cross-linking degree on the morphology of poly(NIPAAm-co-AAc) hydrogels

Hydrogels of poly(N-isopropylacrylamide) co-polymerized with acrylic acid [P(NIPAAm-co-AAc)] were synthesized with cross-linking degrees of 2-7% using (N,N′-methylenebisacrylamide). SEM micrographs revealed that the morphology of dry hydrogels changes from interconnected spherical pores to channel-like pores, with the change in the cross-linking degrees from 3 to 5%. The change in morphology is associated with a significant change in the swelling ratio. It was found that the diffusion rates and permeabilities of methylene blue (MB) through the hydrogel with channel-like pores are significantly higher if the main axes of the pores are oriented parallel to the flow of MB molecules, than if it is oriented perpendicularly. These results show that different morphologies can be obtained by controlling the cross-linking degree of P(NIPAAm-co-AAc) hydrogels in a narrow range around 5% and by performing the polymerization reaction in moulds placed in horizontal and vertical positions, opening a new perspective for modulating their properties in applications as matrices for controlled release of drugs or as membranes for separation processes.     

Synthesis and thermo-responsive behavior of fluorescent labeled microgel particles based on poly(N-isopropylacrylamide) and its related polymers

Poly(N-isopropylacrylamide) (PNIPAM) microgel particles labeled with 3-(2-propenyl)-9-(4-N,N-dimethylaminophenyl)phenanthrene (VDP) as an intramolecular fluorescent probe were prepared by emulsion polymerization. The thermo-responsive behavior of the VDP-labeled PNIPAM microgel particles dispersed in water was studied by turbidimetric and fluorescence analyses. The transition temperature of the VDP-labeled PNIPAM microgel particles in water determined by turbidimetric analysis was ca. 32.5 °C. The wavelength at the maximum fluorescence intensity of the VDP units linked directly to the microgel particles dramatically blue-shifted around the transition temperature. In addition it gradually blue-shifted even below the transition temperature where there was no change observed in the turbidity. These findings suggest that the gradual shrinking of microgel particles occurs with increasing temperature and the subsequent dramatic shrinking results in the increasing in the turbidity. The transition temperatures of VDP-labeled poly(N-n-propylacrylamide) and poly(N-isopropylmethacrylamide) microgel particles determined by turbidimetric analysis were ca. 23 and ca. 42.5 °C, respectively, and their thermo-responsive behavior was similar to that for the VDP-labeled PNIPAM system. In these three systems the microenvironments around the fluorescent probes above the transition temperatures became more hydrophobic than those below the transition temperature, and the estimated values of microenvionmental polarity around the VDP units on their collapsed states were almost the same.     

Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide): synthesis, phase separation and particle formation

Grafting of poly(N-isopropylacrylamide) (PNIPAAm) having carboxylic groups at one end onto poly(allylamine) (PAH) in the presence of water soluble carbodiimide has yielded PAH-g-PNIPAAm copolymers with grafting ratios of 50, 29 and 18, respectively. These thermosensitive copolymers exhibit a lower critical solution temperature (LCST) at 34 °C at a temperature increase cycle regardless of their grafting ratios, a temperature identical to that of PNIPAAm-COOH oligomers. Temperature cycling reveals completely reversible polymer aggregation and dissolution above and below the LCST, respectively. Much smaller particle sizes are observed by scanning force microscopy and transmission electron microscopy compared to dynamic light scattering. A porous sphere model is suggested to depict the structure of the particles formed above the LCST, by which the dependence of the particle sizes on their grafting ratios is interpreted taking into account the surface tension and the spatial aggregation distance. Finally, to demonstrate the capability of the copolymers being used as thermosensitive polyelectrolytes, assembly onto multilayers is conducted and the increase of layer thickness is confirmed by small angle X-ray scattering and ellipsometry characterizations.     

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.     

A quantitative analyses of the viscometric data of the coil-to-globule and globule-to-coil transition of poly(N-isopropylacrylamide) in water

The coil-to-globule and globule-to-coil transition of poly(N-isopropylacrylamide) in aqueous solution had been studied by heating and cooling the sample solution with conventional viscosity measurement. A single chain collapsed globule solution was prepared firstly by adding sodium n-dodecyl sulfate (SDS) into the polymer solution at room temperature, as the chain collapsed to compact globule at higher temperature and then the SDS was removed by electro-dialysis. The viscosity data were analyzed in a quantitative way, which permitted to elucidate the transition temperature and the amount of the water in the collapsed globule precisely.     

Dependence of shrinking kinetics of poly(N-isopropylacrylamide) gels on preparation temperature

Preparation temperature dependence of equilibrium swelling degree and shrinking kinetics of poly(N-isopropylacrylamide) gel has been investigated by optical microscopic measurements. The degree of swelling, d/d₀, at 20 °C was found to be strongly dependent on the preparation temperature, T_prep, where d and d₀ are the diameter of gel during observation and preparation, respectively. The value of d/d₀ was about 1.2 for T_prep=20 °C, but steeply increased by approaching the phase separation temperature ≈32.0 °C. Above 32.0 °C, d/d₀ decreases stepwise to 1.46. This upturn in d/d₀ was correlated with spatial inhomogeneities in gels. That is, the gel became opaque by increasing T_prep. Though the shrinking half-time, t_1/2, of gel was on the order of 500 min for T_prep≤20 °C, t_1/2 decreased to 2 min for T_prep≥26 °C. Hence, a rapid shrinking was attained by simply increasing T_prep. The physical implication of this rapid shrinking in gels was discussed in conjunction with the gel inhomogeneities and a thermodynamic theory of swelling equilibrium.     

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.     

Control of the lower critical solution temperature—type cononsolvency properties of poly(N-isopropylacrylamide) in water—dioxane mixtures through copolymerisation with acrylamide

The behaviour of the homopolymers poly(N-isopropylacrylamide) (PNIPAM), polyacrylamide (PAM) and random copolymers of N-isopropylacrylamide (NIPAM) with acrylamide (AM) was studied by turbidimetry and viscometry in mixtures of water with dioxane. It was found that the well-known lower critical solution temperature-type cononsolvency properties of PNIPAM in water-dioxane mixtures, observed in the water-rich region, can be effectively controlled by copolymerisation of NIPAM with AM. Thus, the cononsolvency properties of the copolymers in water-dioxane mixtures are shifted to higher temperatures and restricted within a narrower solvent composition region as the acrylamide content of the copolymers increases. A significant decrease of the reduced viscosity of the systems exhibiting phase separation properties was observed upon heating, indicative of the collapse of the (co)polymer chains as temperature approaches the corresponding cloud point temperature. Furthermore, when temperature is fixed close to the cloud point temperature, the reduced viscosity decreases with increasing the volume fraction of dioxane, φ, as far as the solvent mixtures are rich in water. On the contrary, the reduced viscosity of PNIPAM in dioxane-rich mixtures is found significantly higher, indicative of an expansion of the polymer chain, as compared to the reduced viscosity of this polymer in the two pure solvents.     

Real-time observation of coil-to-globule transition in thermosensitive poly(N-isopropylacrylamide) brushes by quartz crystal microbalance

Thermosensitive poly(N-isopropylacrylamide) (PNIPAm) brushes grafted on SiO₂-coated quartz crystal surface were prepared by the surface initiated radical polymerization. Using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), about 50 nm thickness of PNIPAm brushes were successfully formed. Quartz crystal microbalance with dissipation (QCM-D) is employed to investigate the collapse and swelling behavior of the PNIPAm brushes in water in real time. Both frequency and dissipation of PNIPAm layer were found to change gradually over the temperature range 15-50 °C, indicating that the brushes undergo a continuous transition. This continuous change is attributed to the nonuniformity and stretching of PNIPAm brushes as well as the cooperativity between collapse and dehydration transition.     

Synthesis and characterization of pH-sensitivity semi-IPN hydrogel based on hydrogen bond between poly(N-vinylpyrrolidone) and poly(acrylic acid)

A novel spherically shaped semi-interpenetrating network (semi-IPN) hydrogel, which is based on hydrogen bond between chemical crosslinked poly(N-vinylpyrrolidone) (PVP) and linear poly(acrylic acid) (PAA), was prepared. The semi-IPN hydrogel was synthesized by three steps: (1) linear PAA with different molecular weights were obtained by a reaction of free radical polymerization used 2,2′-azo-bis-iso-butyronitrile (AIBN) as an initiator; (2) crosslinked PVP bead was obtained by a reaction of N-vinylpyrrolidone with AIBN used as an initiator and N,N′-methylene-bis-acrylamide (NNMBA) used as a crosslinker by the way of suspension polymerization; (3) complexation occurred between suitable amount of aqueous solution of PAA and the porous PVP bead and was stabilized by multiple frost-defrost, from this step the semi-IPN hydrogel was obtained. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) proved the presence of the hydrogen bond in the hydrogel. The swelling behaviour of the hydrogel was studied in buffer solution with different pH and NaCl aqueous solution. The results showed that the semi-IPN hydrogel had excellent pH-sensitivity in the range of pH from 2.25 to 4.00 and the small molecule salt had little influence on the swelling behaviour of the semi-IPN hydrogel over the range of concentration of NaCl aqueous solution investigated. The results were confirmed further by scanning electron microscope (SEM). The mechanism of swelling and deswelling was discussed.     

Simple method for preparation of ultra-thin poly(N-isopropylacrylamide) hydrogel layers and characterization of their thermo-responsive properties

A reactive polymer of N-isopropylacrylamide (co-PNIPAAm) was prepared by copolymerization with a vinyl monomer carrying a protected isocyanate group. Thin layers of co-PNIPAAm were formed on a surface carrying hydroxyl groups using a spin-coater and were cross-linked and immobilized on the surface by heating. These layers were characterized by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, atomic force microscopy and surface plasmon resonance (SPR). The thickness of the co-PNIPAAm layers could be controlled from 4 to 35 nm by changing the concentration of the polymer solutions and the spin-coating conditions. Very little amount of γ-globulin was adsorbed onto the co-PNIPAAm layers even when thicknesses as low as 4 nm were analyzed. In addition, the swelling ratios of the co-PNIPAAm layers were about 4.6 and 1.3 at 25 °C and at 40 °C, respectively. These results indicate that the co-PNIPAAm can be very useful in preparing thermo-sensitive layers on substrates and thus various biomedical applications may be useful.     

Thermo- and pH-sensitive dendrimer derivatives with a shell of poly(N,N-dimethylaminoethyl methacrylate) and study of their controlled drug release behavior

Novel dendrimer derivatives combining the temperature- and pH-sensitivities are synthesized. At first, polyamidoamine (PAMAM) dendrimers with generations 1-5 are synthesized by the reaction of ethylenediamine with methyl acrylate, and then the dendrimers are acylated by chloroacetyl chloride to obtain PAMAM-Cl, which can act as a macroinitiator for further synthesizing functional dendrimers. For fulfilling this goal, the polymers consisting of a dendritic PAMAM core and poly(N,N-dimethylaminoethyl methacrylate) (PDMA) shell are synthesized by atom transfer radical polymerization (ATRP). Their macromolecular structures are characterized by FTIR, ¹H NMR, DSC and particle size analyses, and their aqueous solutions are inspected by UV spectroscopy for understanding their thermo- and pH-sensitivities. The results show that novel dendrimer derivatives exhibit clearly thermo- and pH-respondings in accordance with the change of the environment. Using chlorambucil (CLB) as a model drug, the behaviors of the controlled drug release from polymers with different average graft length of PDMA are studied. The results indicate that the rate of the drug release can be effectively controlled by the pH value.     

Flow and aggregation characteristics of thermo-responsive poly(N-isopropylacrylamide) spheres during the phase transition

To date, a great many researches were focused on improving stimuli-responsive and controlled-release properties of thermo-responsive hydrogel carriers, whereas for the research on flow characteristics during the phase transition, prior reports have not been found. In this paper, poly(N-isopropylacrylamide) (PNIPAM) spheres with thermo-responsive phase transition characteristics were prepared by cross-linked polymerization. In a transparent Pyrex glass pipe with hydrophilic inner wall, flow and aggregation characteristics of PNIPAM spheres during the phase transition from low temperature which was lower than the lower critical solution temperature (LCST) to high temperature (T>LCST) was studied for the first time. Many interesting phenomena about the flow and aggregation behaviors of PNIPAM spheres were found. The velocity of PNIPAM spheres in horizontal pipe decreased from 1.07 cm/s before the phase transition to 0.65 cm/s or even became zero after the phase transition, which is what targeting drug delivery systems desired. When the initial distance was about 5.5 mm at the entrance of testing pipe section, the PNIPAM spheres could aggregate together after the phase transition and subsequently roll forward; but when the initial distance was as large as 8.5 mm, the distance became close at first during the phase transition and then far after the phase transition. Similar results were also found as mentioned above in vertical pipe. When 10 spheres aggregated together, they stopped at a certain position just after the phase transition in horizontal pipe. If the flowrate was more than 40 ml/min, the aggregation configurations such as triangle, tetrahedron, hexahedron and octahedron which formed after the phase transition at flowrate of 20 ml/min disappeared. The results provided valuable information for future applications of thermo-responsive PNIPAM spheres.