Fast synthesis of temperature-sensitive PNIPAAm hydrogels by microwave irradiation

A novel method, microwave irradiation synthesis, is proposed for the preparation of thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The PNIPAAm hydrogels were separately synthesized by using microwave irradiation method and water-bath heating method. Chemical groups, lower critical solution temperature (LCST) and surface morphology of these PNIPAAm hydrogels were characterized by FT-IR, DSC and SEM. Swelling ratios of the gels were measured gravimetrically in the temperature range from 10.0 to 60.0 °C. Results showed that (1) the use of microwave irradiation can greatly shorten the reaction time required for PNIPAAm hydrogel synthesis from several hours to several minutes in comparison with water-bath heating method, and obviously improve the yields of the PNIPAAm gels, which were up to 99% after a short reaction time; (2) SEM micrographs and textural measurement revealed that the gels synthesized using microwave irradiation had more porous structure, and their average pore sizes and specific surface areas were larger than those of the gels synthesized using water-bath heating method; and (3) the PNIPAAm hydrogels synthesized using microwave irradiation had much higher swelling ratios at 10.0 °C below the LCST, and had lower swelling ratio at 60.0 °C above the LCST compared to the hydrogels synthesized by water-bath method.     

Preparation and characterization of a novel IPN hydrogel memberane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAM/CMCS)

A novel type of interpenetrating polymer networks (IPN) hydrogel membrane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAm)/(CMCS) was prepared, and the effects of the feed ratio of components, swelling medium and irradiation dose on the swelling and deswelling properties of the hydrogel was systematically studied. The results showed that the introduction of CMCS did not shift the LCST (at 32 °C), which is similar to the pure PNIPAAm. The lowest swelling ratio was at pH 2. There was little influence of irradiation dose on the thermo- and pH-sensitivity of the IPN hydrogel, increasing dose only decreased the swelling ratio. The PNIPAAm:CMCS=1:4 w/w hydrogel was not thermo-sensitive in distilled water, whereas it showed a discontinuous volume phase transition in pH 2 and a continuous one in pH 8 buffer. Consequently, a combination of pH and temperature can be coupled to control the responsive behavior of these hydrogels.     

Novel poly(N‐isopropylacrylamide)/clay/poly(acrylamide) IPN hydrogels with the response rate and drug release controlled by clay content

Novel interpenetrating network (IPN) hydrogels (PNIPAAm/clay/PAAm hydrogels) based on poly(N‐isopropylacrylamide) (PNIPAAm) crosslinked by inorganic clay and poly(acrylamide) (PAAm) crosslinked by organic crosslinker were prepared in situ by ultraviolet (UV) irradiation polymerization. The effects of clay content on temperature dependence of equilibrium swelling ratio, deswelling behavior, thermal behavior, and the interior morphology of resultant IPN hydrogels were investigated with the help of Fourier transform infrared spectroscopy, differential scanning calorimeter (DSC), scanning electron microscope (SEM). Study on temperature dependence of equilibrium swelling ratio showed that all IPN hydrogels exhibited temperature‐sensitivity. DSC further revealed that the temperature‐sensitivity was weakened with increasing amount of clay. Study on deswelling behavior revealed that IPN hydrogels had much faster response rate when comparing with PNIPAAm/clay hydrogels, and the response rate of IPN hydrogels could be controlled by clay content. SEM revealed that there existed difference in the interior morphology of IPN hydrogels between 20 [below lower critical solution temperature (LCST)] and 50 °C (above LCST), and this difference would become obvious with a decrease in clay content. For the standpoint of applications, oscillating swelling/deswelling behavior was investigated to determine whether properties of IPN hydrogels would be stable for potential applications. Bovine serum albumin (BSA) was used as model drug for in vitro experiment, the release data suggested that the controlled drug release could be achieved by modulating clay content. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 96–106, 2009     

Insulin release behavior of poly(N-isopropylacrylamide-co-N-vinyl-2-pyrrolidone) hydrogel based on modified melamine crosslinkers

Novel hydrogels based on poly(N-isopropylacrylamide-co-N-vinyl-2-pyrrolidone) (PNIPAAm/PNVP), were synthesized by solution radical polymerization using water as solvent and different weight percentage of crosslinkers ranging from 0.5 to 4%. The monomer mol ratios of NIPAAm/VP (0.9/0.1, 0.5/0.5, and 0.1/0.9) were used in all cases. N,N′-methylenebisacrylamide (MBA) and the new synthesized N,N,N-triacrylamido melamine (MAAm) were used as crosslinkers. The swelling parameters such as the swelling ratio Q, equilibrium water content (EWC), volume fraction of polymer φ_p and volume fraction at crosslinking φ_r were calculated from swelling measurements at different temperatures. The lower critical solution temperatures (LCST) of the prepared hydrogels were measured using DSC technique. The data of LCST indicated that the NIPAAm/VP crosslinked with MAAm or MBA showed reversible swelling and shrinking with temperature changes. The temperature dependence of swelling ratio and response kinetics upon heating or cooling was also investigated to understand the smart properties, i.e., temperature sensitive properties of these smart hydrogels. The in vitro release experiments were carried out at 22 and 37°C, respectively, to investigate the effect of temperature-sensitive property of these PNIPAAm/PNVP hydrogels crosslinked with MAAm and MBA crosslinkers on insulin release profiles.     

Synthesis and characterization of temperature-sensitive and biodegradable hydrogel based on N-isopropylacrylamide

Based on a biodegradable cross-linker, N-maleyl chitosan (N-MACH), a series of Poly(N-isopropylacrylamide) (PNIPAAm) and Poly(N-isopropylacrylamide-co-acrylamide) [P(NIPAAm-co-Am)] hydrogels were prepared, and their lower critical solution temperature (LCST), swelling kinetics, equilibrium swelling ratio in NaCl solution, and enzymatic degradation behavior in simulated gastric fluids (SGF) were discussed. The LCST did not change with different cross-linker contents. By altering the NIPAAm/Am molar ratio of P(NIPAAm-co-Am) hydrogels, the LCST could be increased to 39°C. The LCST of the hydrogel was significantly influenced by the monomer ratio of the NIPAAm/Am but not by the cross-linker content. In the swelling kinetics, all the dry hydrogels exhibited fast swelling behavior, and the swelling ratios were influenced by the cross-linker content and NIPAAm/Am molar ratios. Equilibrium swelling ratio of all the hydrogels decreased with increasing NaCl solution concentration. In enzymatic degradation tests, the weight loss of hydrogels was dependent on the cross-linker contents and the enzyme concentration.      

Fast responsive poly(<Emphasis Type="Italic">N,N</Emphasis>-diethylacrylamide) hydrogels with interconnected microspheres and bi-continuous structures

We prepared thermo-responsive polymer hydrogels by γ-ray irradiation of aqueous solutions of N, N-diethylacrylamide at different temperatures below and above its lower critical solution temperature (LCST). Poly(N, N-diethylacrylamide) gel had a transparent and homogeneous structure when the radiation-induced polymerization and crosslinking were carried out below the LCST (25 °C) of the polymer. On the other hand, cloudy and heterogeneous gels were formed at temperatures above the LCST of the polymer (>35 °C). From environmental scanning electron microscopy observations, the gels prepared at 35 and 40 °C were seen to show sponge-like bi-continuous porous structures, while those prepared at 50 °C showed a porous structure consisting of interconnected microspheres. For temperature changes between 10 and 40 °C, gels with porous structures showed rapid volume transitions on a time scale of about a minute, not only for shrinking but also for swelling processes, which is in remarkable contrast to the porous poly(N-isopropylacrylamide) hydrogels.     

Structural characterization of temperature-sensitive hydrogels by field emission scanning electron microscopy (FESEM)

The submicrometer structure of the temperature-sensitive hydrogels was observed by field emission scanning electron microscopy (FESEM), using synthesized hydrogels of different outer size and shape. The hydrogel structure strongly depends on the homogeneity of the polymer chains during the crosslinking process. A porous structure of the poly(vinyl-methyl-ether) (PVME) bulkgel, synthesized by electron beam irradiation of a concentrated polymer solution, was observed in the swollen state because the phase transitions temperature is acquired through the crosslinking process. Photo-crosslinking reaction of the poly(N-isopropylacrylamide) (PNIPAAm) copolymer in the dry state to form PNIPAAm thin films leads to a rather homogeneous structure. In the shrunk state both gels possess structure being more compact than in the swollen state. We also synthesized PVME and PNIPAAm gels with small outer dimensions in the range of some 100 nm. Heating of the thermo-sensitive polymer in diluted solutions collapses the polymer chains or aggregates. The crosslinking reaction (initiated by electron beam or UV irradiation) of these phase separated structures produces thermo-sensitive microgels. These microgel particles of PVME and PNIPAAm are spherical shape having diameters in the range of 30 - 500 nm.     

Synthesis and swelling behavior of thermosensitive hydrogels based on N-substituted acrylamides and sodium acrylate

A series of hydrogels based on N-isopropylacrylamide, sodium acrylate, and N-tert-butylacrylamide were synthesized by free radical polymerization in a mixture of dioxane and water with tetra(ethylene glycol) diacrylate as the crosslinker and benzoyl peroxide as the initiator. The swelling behavior including the swelling rate of the crosslinked gels in water was studied with gravimetric method. The swelling ratio of the gel (0.1 mol% crosslinking) can reach 420 g/g at 20 °C and such a gel can release 96% of the water absorbed at 40 °C. The lower critical swelling temperature (LCST) of the copolymers can be adjusted by changing the chemical composition of the polymers. Such crosslinked gels can be potentially used as thermosensitive superabsorbent because of their high water uptake and thermal sensitivity.     

Swelling and drug releasing properties of poly(N-isopropylacrylamide) thermo-sensitive copolymer gels

A series of N-isopropylacrylamide (NIPAAm) copolymer gels with different hydrophilicities were prepared from NIPAAm, hydrophilic acrylamide (AAm) and hydrophobic butyl methacrylate (BMA). The swelling and thermo-responsive properties of PNIPAAm P (NIPAm-co-BMA) and P(NIPAm-co-AAm) copolymer hydrogels were investigated. The drug loading and releasing behaviors for two kinds of model drug with different hydrophilicities were studied. The result shows that the copolymer gels present negative thermo-sensitivities. The lower critical solution temperature (LCST), equilibrium swelling degree and the initial swelling rate increase as the hydrophilicity of gels increases when the temperature is below the LCST. With increasing gel hydrophilicity the loading ratio for sodium salicylate increases, while for salicylic acid, the reverse is observed. The initial drug releasing rate of sodium salicylate and salicylic acid also increase with increasing gel hydrophilicity. The initial drug releasing rate of sodium salicylate is significantly higher than that of salicylic acid. For salicylic acid which is less hydrophilic, the equilibrium releasing ratio at high temperature is lower than that at low temperature while for sodium salicylate which is more hydrophilic, the equilibrium releasing ratio at high temperature is almost the same as that at low temperature. Equilibrium releasing ratios of the three gels are significantly different from each other for salicylic acid when the temperature is below LCST while the equilibrium releasing ratios of the three gels are all 100% for sodium salicylate. __________ Translated from Journal of Central South University (Science and Technology), 2007, 38(5): 906–911 [译自: 中南大学学报(自然科学版)]     

Effect of the crosslinking level on the properties of temperature‐sensitive poly(N‐isopropylacrylamide) hydrogels

In this study, the effect of the level of crosslinking on the properties of poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels was investigated in terms of their lower critical solution temperature (LCST), interior morphology, equilibrium swelling, and deswelling and swelling kinetics. The thermal analysis showed that PNIPAAm hydrogels, having a wide range of crosslinking levels, exhibited almost the same LCSTs, and this was different from what the conventional theory would have predicted. Scanning electron micrographs revealed that the interior network structure of the PNIPAAm matrix became more porous with an increase in the level of crosslinking. This more porous matrix provided numerous water channels for water diffusion in or out of the matrix and, therefore, an improved response rate to the external temperature changes during the deswelling process and the swelling process. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 582–593, 2003     

Synthesis,thermo-responsive micellization and caffeine drug release of novel PBMA-<Emphasis Type="Italic">b</Emphasis>-PNIPAAm block polymer brushes

Brush-like block copolymers with poly(t-butyl methacrylate) (PBMA) and poly(N-isopropylacrylamide) (PNIPAAm) as side arms, PBMA-b-PNIPAAm, were designed and synthesized via a simple free radical polymerization route. The chemical structure and molecular weight of these polymer brushes were characterized and determined by nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectrometry (FTIR) and gel permeation chromatography (GPC). The micellar formation by these polymer brushes in aqueous solutions were detected by a surface tension technique, and the critical micelle concentration (CMC) ranged from 1.53 to 8.06 mg L⁻¹. The morphology and geometry of polymer micelles were investigated by transmission electron microscope (TEM) and dynamic light scattering (DLS). The polymer micelles assume the regularly-spherical core-shell structure with well-dispersed individual nanoparticles, and the particle size was in the range from 36 to 93 nm. The PNIPAAm segments exhibited a thermoreversible phase transition, so the resulting block polymer brushes were temperature-sensitive and the low critical solution temperature (LCST) was determined by UV-vis spectrometer at about 28.82–29.40°C. The characteristic parameters of the polymer micelles such as CMC, micellar size and LCST values were affected by their compositional ratios and the length of hydrophilic or hydrophobic chains. The evaluation for caffeine drug release behavior of the block polymer micelles demonstrated that the self-assembled micelles exhibited thermal-triggered properties in controlled drug release.     

The synthesis, characterisation, phase behaviour and swelling of temperature sensitive physically crosslinked poly(1-vinyl-2-pyrrolidinone)/poly(N-isopropylacrylamide) hydrogels

Physically crosslinked complexes of polyvinyl pyrrolidinone-poly (N-isopropylacrylamide) (PVP-PNIPAAm) were prepared by photopolymerisation from a mixture of the monomers 1-vinyl-2-pyrrolidinone and N-isopropylacrylamide. IR spectroscopy and calorimetry were used to characterise the resulting xerogels. By alternating the monomer feed ratio, copolymers were synthesised to have their own distinctive lower critical solution temperature (LCST). The transition temperature of the gels was established using cloud point measurement and modulated differential scanning calorimeter (MDSC). This ability to shift the phase transition temperature of the copolymers provides excellent flexibility in tailoring transitions for specific uses. Swelling experiments were performed on the copolymer disks in distilled water at varying temperatures to establish the behaviour of the gels above and below phase transition temperature. The results obtained show that below transition temperature, the gels are water soluble but above this temperature they are slightly less water soluble; significantly less water soluble; or water insoluble; depending on the composition and LCST of the gel.     

Influence of crosslinker and ionic comonomer concentration on glass transition and demixing/mixing transition of copolymers poly(N-isopropylacrylamide) and poly(sodium acrylate) hydrogels

Hydrogels based on N-isopropylacrylamide and sodium acrylate as ionic comonomer were synthesized by free radical polymerization in water using N,N′-methylenebisacrylamide as crosslinker and ammonium persulfate as initiator. The glass transition of dried copolymers poly(N-isopropylacrylamide) (PNIPA) and poly(sodium acrylate) (SA) gels and demixing/mixing transition of PNIPA-SA hydrogels swollen with increasing amounts of water were studied using conventional differential scanning calorimetry. In the crosslinked polymers, the glass transition linearly increases, and the transition range becomes broader, with increasing crosslinker content. Increasing content of ionic comonomer also produces an increase of glass transition temperature, which moves to higher temperatures with higher sodium acrylate fraction. The influence of chemical structure of PNIPA-SA hydrogels on the lower critical solution temperature (LCST) of PNIPA-SA/water mixtures during heating and cooling was quantified as function of the content of the crosslinker and the ionic comonomer, as well as water content of the hydrogel in the range from 95 to 70 wt%. At parity of water content, the LCST occurs at higher temperatures for gels containing higher amounts of sodium acrylate. Similarly, the introduction of N,N′-methylenebisacrylamide causes an increase of the LCST, which grows with increasing of crosslinking degree of the hydrogel.     

Thermo-responsive extraction of cadmium(II) ion with TPEN-NIPA gel. Effect of the number of polymerizable double bond toward gel formation and the extracting behavior

N,N,N′,N′-(Tetrakis-2-pyridylmethyl)ethylenediamine (TPEN) derivatives bearing the different number (1-4) of a double bond moiety on the pyridine ring are synthesized and subjected to copolymerization with N-isopropylacrylamide in the presence of AIBN. The obtained poly(TPEN-NIPA) gels show thermo-responsive swelling/shrinking behaviors and are employed for the extraction of cadmium(II) ion from the aqueous solution to examine the relationship of the gel characteristics and the extraction performance. The polymer gels composed of the TPEN derivative bearing three or four double bonds exhibit temperature-dependent change of swelling and shrinking in water. These gels extract Cd^II ion efficiently from the aqueous solution in the swelling state at 5 °C, while little extraction was observed at 45 °C with shrinking.     

Radiation-grafting of 4-vinylpyridine and N-isopropylacrylamide onto polypropylene to give novel pH and thermo-sensitive films

Here 4-vinylpyridine (4VP) was grafted onto polypropylene films (PP) by mutual irradiation method to give PP-g-4VP; N-isopropylacrylamide (NIPAAm) was then grafted onto the PP-g-4VP films to give (PP-g-4VP)-g-NIPAAm by pre-irradiation method, using a ⁶⁰Co γ-source. The dependence of grafting percentage on radiation dose, temperature, reaction time, and monomer concentration was studied. (PP-g-4VP)-g-NIPAAm films were characterized by infrared spectroscopy (FTIR-ATR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The critical pH point and lower critical solution temperature (LCST) were determined by swelling and water contact angle measurements. The LCST also was determined by DSC. The binary graft copolymer films are shown to be thermo-pH sensitive.     

Temperature and pH dual stimuli responsive PCL‐b‐PNIPAAm block copolymer assemblies and the cargo release studies

A new atom transfer radical polymerization (ATRP) initiator, namely, 2‐(1‐(2‐azidoethoxy)ethoxy)ethyl 2‐bromo‐2‐methylpropanoate containing both “cleavable” acetal linkage and “clickable” azido group was synthesized. Well‐defined azido‐terminated poly(N‐isopropylacrylamide)s (PNIPAAm‐N₃)s with molecular weights and dispersity in the range 11,000–19,000 g mol^?1 and 1.20–1.28, respectively, were synthesized employing the initiator by ATRP. Acetal containing PCL‐b‐PNIPAAm block copolymer was obtained by alkyne–azide click reaction of azido‐terminated PNIPAAm‐N₃ with propargyl‐terminated PCL. Critical aggregation concentration (CAC) of PCL‐b‐PNIPAAm copolymer in aqueous solution was found to be 8.99 × 10^?6 M. Lower critical solution temperature (LCST) of PCL‐b‐PNIPAAm copolymer was found to be 32 °C which was lower than that of the precursor PNIPAAm‐N₃ (36.4 °C). The effect of dual stimuli viz . temperature and pH on size and morphology of the assemblies of PCL‐b‐PNIPAAm block copolymer revealed that the copolymer below LCST assembled in spherical micelles which subsequently transformed to unstable vesicles above the LCST. Heating these assemblies above 40 °C led to the precipitation of PCL‐b‐PNIPAAm block copolymer. Whereas, at decreased pH, micelles of PCL‐b‐PNIPAAm copolymer disintegrate due to the cleavage of acetal linkage and precipitation of hydrophobic hydroxyl‐terminated PCL. The encapsulated pyrene release kinetics from the micelles of synthesized PCL‐b‐PNIPAAm copolymer was found to be faster at higher temperature and at lower pH. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 1383–1396     

Fast responsive poly(N-isopropylacrylamide) hydrogels prepared in phenol aqueous solutions

Fast responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with improved properties were prepared in phenol aqueous solutions with different concentrations. Due to the expanded network structure in water, the resulted hydrogels are capable of absorbing a large amount of water, i.e. exhibits a much increased swelling ratio at room temperature. Importantly, the hydrogels demonstrated much faster response rate than that of traditional PNIPAAm hydrogel upon external temperature increase.     

Effect of filler networking on the response of thermosensitive composite hydrogels

Several composite hydrogels of poly(N-isopropylacrylamide) (pNIPAAm) with sodium montmorillonite (NaMM) have been synthesized using a fixed polymer/NaMM ratio (4:1 wt./wt.), but various monomer concentrations, in order to obtain hydrogels with different degrees of swelling, and thus different clay contents in the swollen state. For comparison, unfilled pNIPAAm gels have been also prepared at the same concentrations. The equilibrium swelling behaviour of the gels has been studied both in the swollen and in the shrunk state. In the swollen state, the polymer volume fraction increases with the initial monomer concentration C₀. In the shrunk state, the polymer fraction in pNIPAAm hydrogels is dependent on the specimen size and on C₀, whereas in the composite gels a constant polymer content is observed. When subjected to stepwise heating from 25 to 45 °C, unfilled gels undergo only poor deswelling. By contrast, complete deswelling takes place in composite gels. The latter show half-shrinking times varying over two orders of magnitude, depending on the monomer concentration and on the procedure followed to disperse NaMM, which determine the overall dispersion state of the filler, as evidenced by transmission electron microscopy (TEM). In particular, TEM observations show clay networking above a percolation threshold near 2.5 wt.% of NaMM. The effect of the incorporation of clay on the response to thermal stimuli is discussed in terms of the ability of NaMM to hinder the hydrophobic association of pNIPAAm segments and in terms of its dispersion state. It is suggested that, above the percolation threshold, NaMM forms a hydrophilic, physical network, through which water can flow also above the volume transition temperature, where pNIPAAm acquires a hydrophobic character.     

Structural observation of heterogeneous poly(N-isopropyl acrylamide-co-acrylic acid) hydrogels in highly hydrated states

Heterogeneous hydrogels were prepared by -ray irradiation of aqueous solutions of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) having various compositions above the lower critical solution temperature. The structures of the poly(N-isopropylacrylamide) (PNIPAAm) gel and poly(NIPAAm-co-AAc) gels in both their highly hydrated and their natural states were observed by environmental scanning electron microscopy. The heterogeneous structures of the homopolymer gel and the copolymer gels whose AAc contents were between 10–50% consisted of interconnected microspheres. In the copolymer gel with a high AAc content, the structure became a largely interconnected one which lacked micro-droplets. The hydrophobic interaction caused by hydrogen bonding between the unionized carboxylic acid groups of AAc and the amide groups of NIPAAm, the rates of polymerization, and the aggregation rates play important roles in the formation of interconnected microsphere gel structures.     

Preparation of a thermo- and pH-sensitive nanofibrous scaffold with embedded chitosan-based nanoparticles and its evaluation as a drug carrier

Environmentally sensitive poly(N-isopropylacrylamide) (PNIPAAm) nanofibrous scaffolds loaded with a hydrophilic drug were fabricated via an electrospinning process. First, thermally crosslinkable poly(NIPAAm-co-N-methylolacrylamide) (PNN) was synthesized by redox polymerization below the phase transition temperature of PNIPAAm. The phase transition temperature of the PNN copolymer could be altered from 34 to 40 °C by changing the ratio of N-methylolacrylamide (NMA) to NIPAAm. Subsequently, PNN/chitosan nanofibers were electrospun using ethanol/acetic acid/water as a cosolvent. The PNN/chitosan nanofibers were sensitive to both pH and temperature. The fibrous structure of the soaked PNN/chitosan nanofibers was successfully preserved by the crosslinking of NMA. Furthermore, the chitosan-based nanoparticles (NPs) were introduced into the PNN nanofibers (PNN/NPs) to achieve prolonged drug release. The nanoparticles were observed in the PNN nanofibers by transmission electron microscopy. All of the scaffolds examined had high tensile strengths (1.45 MPa or above) and exhibited no significant cytotoxicity toward human fetal skin fibroblasts. Finally, doxycycline hyclate was used as a model drug. The results illustrated that PNN/NPs nanofibrous scaffolds exhibited continuous drug release behavior for up to 1 week, depending on the pH and temperature.