Transport of ionizable drugs and proteins in crosslinked poly(acrylic acid) and poly(acrylic acid-co-2-hydroxyethyl methacrylate) hydrogels. I. Polymer characterization

The purpose of this investigation was to define the polymer structure and elucidate the swelling behavior of ionizable hydrophilic polymers (hydrogels) in water and buffered media. Poly(acrylic acid) (PAA) and poly(acrylic acid-co-2-hydroxyethyl methacrylate) [P(AA-co-HEMA)] hydrogels were synthesized with varying degrees of hydrophilicity and crosslinking and were designed as potential bioadhesive controlled-release dosage forms. The thermal initiation procedure employed during polymerization was optimized to eliminate unreacted residuals. Equilibrium and dynamic swelling studies were undertaken to determine the polymer mesh size and molecular weight between crosslinks of the hydrogels in the ionized and nonionized states. The PAA hydrogel mesh sizes ranged from 100 to 400 Å over pH values of 3–7, whereas the P(AA-co-HEMA) hydrogel mesh sizes were between 13 and 140 Å. These results demonstrated the significance of the swelling medium pH on the hydrated state of the polymers relative to crosslinking or copolymerization composition. © 1996 John Wiley & Sons, Inc.     

Dual stimuli responsive neutral/cationic polymers/clay nanocomposite hydrogels

In this work, a thermodynamic-based equilibrium-swelling model was proposed to predict the swelling process of neutral/cationic polymers-clay nanocomposite hydrogels sensitive to dual stimuli temperature and pH. Indeed, the new swelling model can estimate the effect of the rigid clay nanoparticles component on swelling behavior of blend nanocomposite hydrogels. The mixing term in model was developed based on lattice theory by considering the effects of solvent-polymers, solvent-clay, and polymer-clay interaction parameters. The influence of the ionic groups of the clay layers and cationic polymer on the swelling was also taken into account in the proposed model. The model was verified by preparation of polyvinyl alcohol/chitosan/montmorillonite intelligent nanocomposite hydrogel by tripolyphosphate crosslinking method followed by freezing–thawing process. It was found that it could give good prediction for the equilibrium swelling of polymer-clay nanocomposite hydrogels in the case of phantom network, especially where the swelling temperature and clay loading level are high and the pH of swelling medium is low. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48797.     

HES-HEMA nanocomposite polymer hydrogels: swelling behavior and characterization

Organophilic sodium montmorillonite (Na-MMT) and Laponite-RD clays were incorporated into photopolymerizable hydroxyethyl starch (HES) modified with 2-hydroxyethyl methacrylate (HEMA). Swelling, mechanical properties and thermal stability of obtained crosslinked nanocomposite polymers were evaluated. A camphorquinone-amine system was used as photoinitiating system in visible light. The interaction between nano-sized filler particles and polymer hydrogel was evaluated by FT-IR spectroscopy and the platelet distribution was investigated by SEM. An increased thermal stability of nanocomposite polymers upon addition of clay was observed by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) indicating interaction between the clay platelets and the polymer chains. The crosslinking density for HES-HEMA/MMT nanocomposite hydrogels as investigated by swelling measurements increases with increasing the organo-clay content. The mechanical properties of virgin hydrogels were improved by the introduction of organo-clay as evidenced by oscillation rheology measurements. Whereas, the increase in crosslink density and storage modulus with clay content for laponite was found to be increasing for all concentrations investigated, for MMT there is an optimum content of ca. 1.5 wt%.     

Synthesis and evaluation of swelling kinetics of electric field responsive poly(vinyl alcohol)‐g‐polyacrylic acid/OMNT nanocomposite hydrogels

Novel electro‐responsive nanocomposite hydrogels were prepared by the radical graft polymerization reaction of partially neutralized acrylic acid on poly(vinyl alcohol) and organically modified MMT nanoclay (OMMT) using glutaraldehyde as a crosslinker and potassium initiator. The structures of the hydrogels were confirmed by using Fourier transform infrared, X‐ray diffraction, and scanning electron microscopy study. The nanocomposite hydrogels were characterized by evaluating such molecular weight between crosslinks, (Mc) crosslinking density (ρ), and mesh size (ξ). The effects of various parameters on the swelling behavior of the hydrogels were studied. The thermogravimetric analysis indicated that introduction of clay resulted in an increase in thermal stability. Finally, the electric stimuli responsive measurement indicates the bending of hydrogel toward the cathode in an aqueous solution of NaCl. POLYM. COMPOS., 36:34–41, 2015. © 2014 Society of Plastics Engineers     

A promising porous polymer-nanoclay hydrogel nanocomposite as water reservoir material: synthesis and kinetic study

A porous hydrogel nanocopmposite based on biodegradable salep and montmorillonite (MMT) was synthesized by in-situ free radical graft polymerization of salep chains with acrylic acid (AA) monomers. The chemical structure and morphological properties of the prepared hydrogels was evaluated by FTIR spectroscopy, X-ray diffraction and SEM techniques. The effect of reaction variables such as crosslinker, initiator, monomer and clay contents on equilibrium water absorption capacity and swelling kinetic of hydrogel were investigated and optimized. Swelling behavior of the hydrogels in various pH and saline solutions was also studied. Incorporation of MMT into hydrogel matrix caused the formation of porous hydrogel network. These porous structures resulted in higher water uptake capacity and swelling rate in hydrogel nanocomposite in comparison to neat hydrogel sample. Moreover, hydrogel nanocomposite sample exhibited proper salt and pH-sensitive behavior. High swelling capacity and rate, porosity, salt and pH sensitivity make hydrogel nanocomposite a profitable candidate in agricultural and horticultural applications, such as water reservoir system.     

PH-induced structure change of poly(vinyl alcohol) hydrogel crosslinked with poly(acrylic acid)

The structure of the hydrogel of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) was investigated by small angle X-ray scattering (SAXS) of synchrotron radiation. A physically crosslinked blend gel, which was prepared by repetitive freezing and thawing of an aqueous solution of PVA and PAA, could be chemically crosslinked by esterfication of PVA with PAA even in the hydrogel state. The chemical crosslinking induced the destruction of physical crosslinks into a folded structure, indicating that the chemical crosslinking proceeds at the sites around the physical crosslinks that contain PVA and PAA in much higher concentration than other portion of the gel. The pH-induced structure changes of the PVA hydrogels, chemically crosslinked with poly(acrylic acid) (PAA) were investigated by SAXS on the samples of various chemical crosslinking time. The gels were shrunk at pH4, and swollen at pH8. The results of SAXS showed, that the Porod slope changed with chemical crosslinking time from -3.5 to ?2.9 at pH4, and from ?2.9 to ?2.4 at pH8. The results suggest that a folded structure as a structural domain, which is characterized by fractally rough interface, tends to change into the structure that corresponds to percolation cluster, particularly at pH8. The gels immersed in pH8 showed a remarkable structure change accompanying swelling. The results revealed that a conformational change of PAA chains, induced by the pH change, can be explained by the presence of a structural domain in the gel network, where both PVA chains and PAA chains get entangled and partially form a interpenetrating polymer network(IPN).     

Swelling and auramine-<Emphasis Type="Italic">O</Emphasis> adsorption of carboxymethyl cellulose grafted poly(methyl methacrylate)/Cloisite 30B nanocomposite hydrogels

Carboxymethyl cellulose (CMC) grafted poly(methyl methacrylate)/Cloisite 30B nanocomposite hydrogels were prepared for adsorptive removal of auramine-O (as a cationic dye model) from wastewater. For the synthesis of nanocomposite hydrogel by free radical polymerization method, potassium persulfate (KPS), methyl methacrylate (MMA), N,N′-methylene bisacrylamide (MBA) and Cloisite 30B were used as initiator, monomer, cross-linker and nano-filler, respectively. The nanocomposite hydrogels were characterized by FTIR, TGA, SEM and XRD techniques. The FTIR results showed that the monomer was grafted onto carboxymethyl cellulose chains successfully. Swelling behavior of nanocomposite hydrogel as a function of KPS, MBA, MMA concentration and CMC/Cloisite 30B weight ratio was studied by Taguchi method using Minitab 16 software. According to ANOVA results, the most effective factor of equilibrium swelling of nanocomposite hydrogel was CMC/Cloisite 30B weight ratio. Addition of Cloisite 30B to hydrogel up to a certain amount improved swelling, though its high amount decreased swelling. The effects of pH and ionic strength on swelling of optimum hydrogels were investigated. Maximum swelling of nanocomposite hydrogel occurred at pH 7.0. The kinetic data of adsorption fitted well to pseudo-second-order model. The best isotherm for investigation of adsorption mechanism was Langmuir model suggesting the formation of a monolayer on the adsorbent surface. FTIR results, before and after auramine-O adsorption, showed that complexation is the main mechanism of adsorption. High adsorption capacity of nanocomposite hydrogels made them more efficient in wastewater treatment application.     

Hydrogels reinforced with nanoclays with improved response rate

Two series of semiinterpenetrating networks (SIPN) based on linear hydrophilic poly(vinyl alcohol) (PVA) and thermo‐responsive poly(N‐isopropylacrylamide) (PNIPA), physically crosslinked with inorganic clay, are presented. The hydrogels with different crosslinking densities were prepared by varying the content of clay from 1 to 6 wt % and contained linear interpenetrant, PVA in the range of 0.5–1.5 wt %. The effect of clay content on swelling/deswelling behavior and phase transition in PNIPA gels, as well as the feasibility of reinforcing the gels with high molecular weight PVA, were analyzed. The thermal response of hydrogels, followed by DSC, confirmed that the insertion of hydrophilic PVA did not have a significant effect on the onset of the volume phase transition temperature, while the response was faster. The equilibrium degree of swelling of SIPNs and PNIPA hydrogels was in the range of 9–79 and decreased with increasing content of clay. The internal morphology and surface wettability of the hydrogels were investigated by scanning electron microscope analysis and contact angle measurements, respectively. The network structural parameters of the PNIPA and SIPN nanocomposites hydrogels, such as the average molecular weight between crosslinks, M_c, and effective crosslinking density, N_e, were determined by dynamic mechanical analysis. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44535.     

Unusual swelling behavior of polymer-clay nanocomposite hydrogels

The swelling behavior and the elastic properties of nanocomposite hydrogels have been investigated. The hydrogels were prepared by free-radical polymerization of the monomers acrylamide (AAm), N,N-dimethylacrylamide (DMA), and N-isopropylacrylamide (NIPA) in aqueous clay suspensions at 21 °C. Laponite with a radius of gyration in distilled water of 20 nm was used as clay particles in the hydrogel preparation. The reactions with AAm monomer were carried out in the presence of the chemical crosslinker N,N′-methylenebis(acrylamide) (BAAm). It was found that the volume of nanocomposite hydrogels immersed in water rapidly increases and attains a maximum value after about one day. Surprisingly, further increase in the swelling time results in the deswelling of the gels until they reach a limiting swelling ratio after about 5 days. This unusual swelling behavior is observable only when the clay concentration in the hydrogel is above the overlap threshold c^∗. Swelling measurements combined with the elasticity tests show that the effective crosslink density first decreases, but then increases with increasing time of swelling of the hydrogels. The results were explained in terms of the rearrangements of the highly entangled polymer chains and clay particles during the gel volume change.     

Evaluation of a nanocomposite hydrogel for water shut‐off in enhanced oil recovery applications: Design,synthesis, and characterization

This work involves the synthesis of a nanocomposite hydrogel from just polymer and clay without the use of conventional organic crosslinkers. Conventional hydrogel design usually involves a multicomponent reaction that incorporates monomer (or polymer), initiator, and an organic crosslinker. However, because of the many limitations, setbacks, and inconsistencies involved with organic crosslinkers, authors herein present a nanocomposite hydrogel that incorporates polymer and clay only. It was found that these hydrogels show surprising mechanical toughness, tensile moduli, and tensile strengths. Study of gel behavior reveal physical interaction between polymer and clay, due in part to adsorption of polymer chains onto clay surface and ionic interactions between anionic carboxylate groups of polymer chains and positive clay surface. X‐ray diffraction patterns and Scanning Electron Microscopy revealed the formation of intercalated and exfoliated clay morphology. Increase in clay concentration and gel strength had a direct proportionality. The effect of clay concentration on hydrogel decomposition temperature was also reported by thermogravimetric analysis. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Comparison the properties of PVA/Na+‐MMT nanocomposite hydrogels prepared by physical and physicochemical crosslinking

A novel physicochemical crosslinked nanocomposite hydrogel based on polyvinyl alcohol (PVA) and natural Na‐montmorillonite (Na⁺‐MMT) was synthesized by chemical crosslinking of nanocomposite hydrogel followed by a freezing‐thawing process. The effects of physical crosslinking, as well as physicochemical crosslinking, on the structure, morphology, and properties (thermal, mechanical, swelling, and deswelling) of nanocomposite hydrogels were investigated and compared with each other. The structure and morphology of nanocomposites were studied by Fourier transform infrared, X‐ray diffraction, field emission scanning electron microscopy, and transmission electron microscopy techniques. The thermal and mechanical properties of nanocomposites that were affected by physical and physicochemical crosslinking were evaluated by thermogravimetric analysis, differential scanning calorimeter, dynamic mechanical analysis, hardness test, and Water vapor transmission rate (WVTR) experiments. The results showed that the physicochemical crosslinking of a PVA nanocomposite leads to a reduction in crystallinity and melting temperature, as well as an increase in the Hardness and WVTR compared to a physically crosslinked PVA nanocomposite hydrogel. The swelling and deswelling experiments were performed using a gravimetric method, and it was shown that controlled crosslinking of PVA nanocomposite hydrogel with glutaraldehyde causes the swelling ratio to increase and the cumulative amount of water loss to decrease. The swelling (sorption) and deswelling (desorption) kinetics data for physically and physicochemical crosslinking of nanocomposite hydrogels were fitted with a fickian model. It is concluded that through control crosslinking of PVA nanocomposite can lead to a hydrogel with higher swelling capacity than that is in conventional PVA nanocomposite hydrogel. POLYM. COMPOS., 37:897–906, 2016. © 2014 Society of Plastics Engineers     

SWELLING PROPERTIES OF POLY(N-VINYLIMIDAZOLE) HYDROGELS

The swelling capacity of poly(N-vinylimidazole) hydrogels in aqueous solutions and organic solvents was measured as a function of polymer network structure. In pure water, the swelling capacity decreases monotonously upon increasing the crosslinker ratio and the total comonomers concentration in the polymerization feed mixture. In methanol a similar behaviour was observed while in ethanol, the swelling capacity shows an abrupt change from large values to 0.01 grams of water per gram of dry gel, that is to say, PVI experience swollen-collapsed transitions with small changes of the gel crosslinking degree. Molecular weight of chains between crosslinks, determined from swelling measurements in methanol, scales with the product of the crosslinker and total comonomers concentrations in the feed mixture to m1.14-0.05. The dependence of the polymer solvent interaction parameter on the polymer concentration inside the swollen gel was also determined for water and ethanol.     

Preparation and characterization of polyacrylic acid‐poly(vinyl alcohol)‐based interpenetrating hydrogels

Some structural features of hydrogels from poly(acrylic acid) (PAAc) of various crosslinking degrees have been investigated through mechanical and swelling measurements. Interpenetrating polymer hydrogels (IPHs) of poly(vinyl alcohol) (PVA) and PAAc have been prepared by a sequential method: crosslinked PAAc chains were formed in aqueous solution by crosslinking copolymerization of acrylic acid and N,N‐methylenebisacrylamide in the presence of PVA. The application of freeze–thaw (F–T) cycles leads to the formation of a PVA hydrogel within the synthesized PAAc hydrogel. The swelling and viscoelastic properties of the IPHs were evaluated as a function of the content of crosslinker and the application of one F–T cycle. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5789–5794, 2006     

A comparative study of swelling properties of hydrogels based on poly(acrylamide‐co‐methyl methacrylate) containing physical and chemical crosslinks

Poly (acrylamide‐co‐methyl methacrylate) hydrogels of different ratios were prepared by using chemical and physical crosslinks to study the effect of nature of crosslinks on swelling behavior of hydrogels. The chemically crosslinked gels were prepared by using NN′‐methylene bis acrylamide, while physically crosslinked hydrogels were prepared by precipitation polymerization method, using dioxane as solvent. Detailed swelling kinetics such as swelling ratio, transport exponent n, diffusion coefficient D and the effect of pH on equilibrium swelling studies. The study revealed that the nature of crosslinks alter the swelling characteristics of the hydrogel. In chemically crosslinked hydrogels the water transport is Fickian in nature, while in the case of the physically crosslinked hydrogels the water transport mechanism is anomalous indicating major change in relaxation mechanism due to nature of crosslinks. The results also indicate that with increasing acrylamide content the swelling ratio of the hydrogels were also increased, but the transport exponent n remains nearly constant. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 779–786, 2003     

Preparation,characterization, and water‐sorption study of polyvinyl alcohol based hydrogels with grafted hydrophilic and hydrophobic segments

The interpenetrating polymer network hydrogels based on poly(vinyl alcohol) were obtained by graft copolymerization of acrylamide and styrene onto polyvinyl alcohol in the presence of N,N′‐methylene bisacrylamide as a crosslinking agent. The hydrogels were characterized by optical microscopy, scanning electron microscopy, infrared spectral analysis, differential scanning calorimeter, and thermogravimetric analysis. The hydrogels showed enormous swelling in aqueous medium and displayed swelling characteristics, which were highly dependent on the chemical composition of the hydrogels and pH of the swelling medium. The kinetics of water uptake and the mechanisms of water transport were studied as a function of composition of the hydrogel and pH of the swelling medium. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 95: 1129–1142, 2005     

Synthesis and swelling properties of pH‐ and temperature‐sensitive interpenetrating polymer networks composed of polyacrylamide and poly(γ‐glutamic acid)

Novel hydrogels of interpenetrating polymer networks (IPNs) composed of polyacrylamide and poly(γ‐glutamic acid) were synthesized. In these systems, both polymers were crosslinked independently; this reduced the potential loss of a polymer during the washing process, as often occurs in semi‐IPN systems. Interpolymer interactions were investigated with Fourier transform infrared spectroscopy and differential scanning calorimetry. These studies suggested possible interactions between both polymers by the formation of hydrogen bonds. The swelling behavior of these hydrogels was analyzed by immersion of the hydrogel samples in deionized water at 25 and 37°C and in buffer solutions with pHs of 3, 7, and 10. The kinetics of swelling showed increases in the values of the swelling ratio with increasing immersion time in the swelling medium, molar proportion of the biopolymer in the hydrogel, temperature, and pH of the swelling medium. All of the hydrogels swelled rapidly and reached equilibrium in an average time of 40 min. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

聚（N-异丙基丙烯酰胺）／海藻酸钠／粘土复合水凝胶的制备及溶胀动力学研究

以无机粘土为交联剂制备了聚（N-异丙基丙烯酰胺）／海藻酸钠／粘土（PINPA／SA／Clay）复合水凝胶,通过红外光谱、X射线衍射对凝胶的结构进行了表征,结果表明：粘土的结晶结构已被破坏,粘土规整的片层被剥离并在凝胶中无序分布,起到交联剂的作用;随粘土含量的增加,凝胶网络交联密度增加,溶胀速度下降。在不同温度下对不同粘土含量的凝胶进行了溶胀动力学测试,表明在低于其相转变温度时,凝胶的扩散类型为non－Fickian扩散。     

Semi‐interpenetrating polymer network hydrogels based on aspen hemicellulose and chitosan: Effect of crosslinking sequence on hydrogel properties

Semi‐interpenetrating network hydrogel films were prepared using hemicellulose and chemically crosslinked chitosan. Hemicellulose was extracted from aspen by using a novel alkaline treatment and characterized by HPSEC, and consisted of a mixture of high and low molecular weight polymeric fractions. HPLC analysis of the acid hydrolysate of the hemicellulose showed that its major constituent sugar was xylose. X‐ray analysis showed that the relative crystallinity of hydrogels increased with increasing hemicellulose content up to 31.3%. Strong intermolecular interactions between chitosan and hemicellulose were evidenced by FT‐IR analysis. Quantitative analysis of free amino groups showed that hemicellulose could interrupt the chemical crosslinking of chitosan macromolecules. Mechanical testing and swelling experiments were used to define the effective network crosslink density and average molecular weight between crosslinks. Swelling ratios increased with increasing hemicellulose content and mainly consisted of H‐bonded bound water. Results revealed that by altering the hydrogel preparation steps and hemicellulose content, crosslink density and swelling behavior of semi‐IPN hydrogels could be controlled without deteriorating their mechanical properties. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

温度及pH敏感共聚/粘土纳米复合水凝胶的合成与性能研究

以无机粘土为交联剂制备了具有温度、pH双重敏感性的聚（N-异丙基丙烯酰胺-co-甲基丙烯酸-β-羟乙酯）/粘土纳米复合水凝胶（P（NIPA-co-HEMA）/clay）,并用红外和X衍射对其结构和形态进行了表征。在弱碱性（pH=7.4）和25℃条件下,分别研究了温度和不同pH缓冲溶液对该凝胶溶胀度的影响,测定了纳米复合水凝胶的力学性能。结果表明：水凝胶的粘土已被剥离成单片层,且均匀分散在凝胶网络中,起交联作用;P（NIPA-co-HEMA）/clay具有良好的温度、pH双重敏感特性;凝胶的断裂伸长率〉1000%。     

通过RAFT聚合方法合成具有高强度和高溶胀率的纳米水凝胶

为了得到具有高强度和高溶胀率的纳米水凝胶(NCgels),N-异丙基丙烯酰胺通过可逆加成断裂链转移(RAFT)聚合的方法,插层在含有质量分数为0.25%～15%的可扩展的有机化的蒙脱土(Clay-S)层间并交联。结果表明,与传统水凝胶相比,该水凝胶的强度和溶胀性能得到了很大提高,并且对温度的变化具有较快的响应速率。以质量分数为5%的蒙脱土,链转移剂的质量分数为0.5%制备的纳米水凝胶为例,该水凝胶在20℃的溶胀率为450,而传统水凝胶在相同温度时的溶胀率仅为20;该水凝胶在1min内失去75%的水,在4min内失去约90%的水,而传统水凝胶在15min内仅失去66%左右的水。