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     

Sustained release behavior of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogels containing activated carbon fibers

The composites of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogel and activated carbon fibers (ACFs) were prepared as sustained drug release system with excellent mechanical properties. The mechanical properties of hydrogels were improved greatly by addition of ACFs. The thinner ACFs were more effective in increasing the mechanical properties of composite hydrogels. The cumulative amount of release and the release period were dependent on the surface area and the pore volume of ACFs. The drug release was maximized at basic condition due to the pH‐sensitive hydrogel matrices and the initial bust phenomenon was alleviated by incorporating ACFs in the hydrogels. The drug release was sustained about four times longer and the mechanical property was increased about 2.6 times higher because ACFs worked as drug reservoir and reinforcement. Cytotoxicity evaluation confirmed the biocompatible characteristics of the ACFs‐containing hydrogels. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and swelling behavior of biodegradable hydrogels based on α,β‐poly(N‐2‐hydroxyethyl‐DL‐aspartamide)

Biodegradable polymers and the hydrogels have been increasingly applied in a variety of biomedical fields and pharmaceutics. α,β‐Poly(N‐2‐hydroxyethyl‐DL ‐aspartamide), PHEA, one of poly(amino acid)s with hydroxyethyl pendants, are known to be biodegradable and biocompatible, and has been studied as an useful biomaterial, especially for drug delivery, via appropriate structural modification. In this work, hydrogels based on PHEA were prepared by two‐step reaction, that is, the crosslinking of polysuccinimide, the precursor polymer, with oligomeric PEG or PEI‐diamines and the following nucleophilic ring‐opening reaction by ethanolamine. Soft hydrogels possessing varying degrees of gel strength could be prepared easily, depending on the amount of different crosslinking reagents. The swelling degrees, which were in the range of 10–40 g–water/dry gel, increased somewhat at higher temperature, and also at alkaline pH of aqueous solution. A typical hydrogel remained almost unchanged for 1 week, at 37°C in phosphate buffer of pH 7.4, and then seemed to degrade slowly as time. A porous scaffold could be fabricated by the freeze drying of water‐swollen gel. The PHEA‐based hydrogels have potential for useful biomaterial applications including current drug delivery system. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3741–3746, 2003     

γ‐Irradiation preparation of poly(acrylic acid)–chitosan hydrogels for in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a γ‐irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid (AAc) content increased. The equilibrium swelling studies of hydrogels prepared under various conditions were carried out in an aqueous solution, and the pH sensitivity in a range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30 kGy dose of radiation. In addition, an increase of the degree of swelling with an increase in the pH was noticed and it had the highest value at pH 12. The drug 5‐fluorouracil was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at intestinal pH and the rest of the drug was released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3270–3277, 2003     

Synthesis and characterization of cetirizine‐containing,pH‐sensitive acrylic acid/poly(vinyl alcohol) hydrogels

In this study, interpenetrated acrylic acid (AA)/poly(vinyl alcohol) (PVA) hydrogels were prepared by free‐radical polymerization with N,N‐methylene bisacrylamide (MBAAm) as a crosslinker. The basic structural parameters, such as the molecular weight between crosslinks, volume interaction parameter, number of crosslinks, Flory–Huggins solvent interaction parameter, and diffusion coefficient, were calculated. Cetirizine dihydrochloride was loaded as a model drug in selected samples. The prepared hydrogels were evaluated for swelling, sol–gel fraction, and porosity. The swelling of the AA/PVA hydrogels was found to be directly proportional to the pH, that is, 1.2–7.5, depending on composition. The percentage of cetirizine hydrochloride was found to be directly proportional to the buffer pH and was at its maximum at pH 7.5, that is, 90–95%, and its lowest at pH 1.2, that is, 20–30%. The gel fraction increased with increasing concentration of AA and MBAAm, whereas the porosity showed the same response with AA, but an inverse relationship was observed with MBAAm. The drug‐release data were fitted into various kinetics models, including the zero‐order, first‐order, Higuchi, and Peppas models, which showed non‐Fickian diffusion. The prepared hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy, and no interaction was found among the polymer ratio and the drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43407.     

Preparation and characterization of thermo‐sensitive poly(vinyl alcohol)‐based hydrogel as drug carrier

Poly(vinyl alcohol)s (PVA) with high and low molecular weights were chemically modified by introducing acetaldehyde onto the polymer backbone to induce thermal‐responsive properties. The influence of both molecular weight ( ) and acetalization degree on the lower critical solution temperature (LCST) of thermo‐sensitive polymer was investigated. Moreover, a temperature responsive hydrogel was prepared by controlled cross‐linking of acetalized poly(vinyl alcohol) (APVA) and glutaraldehyde. As a model drug, ciprofloxacin was introduced into the prepared thermal sensitive hydrogel to reveal the drug loading and release behaviors. The structure, thermo‐sensitivity, swelling/deswelling kinetics, morphology, and drug loading/release behaviors were also investigated. The results indicated that the APVA polymer solution exhibited temperature responsivity, and APVA with high acetalization degree showed low LCST, whereas those with high PVAs showed high LCST. Meanwhile, morphology study was identical with the swelling/de‐swelling behavior. The loading and release of ciprofloxacin were controllable. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39720.     

Polyelectrolyte complex hydrogel composed of chitosan and poly(γ‐glutamic acid) for biological application: Preparation,physical properties,and cytocompatibility

Polyelectrolyte complex (PEC) hydrogels composed of chitosan as a cationic polyelectrolyte and poly (γ‐glutamic acid) (γ‐PGA) as an anionic polyelectrolyte were prepared from PEC dispersions based on a chitosan solution to which different amounts of γ‐PGA solutions were added to charge equivalency. The chemical structures of the PEC hydrogels were investigated by Fourier transform infrared spectroscopy. The physical properties, fixed charge concentration, crystallinity, mechanical properties, micromorphology, and swelling properties of the PEC hydrogels were also investigated. The total fixed charge concentration of the PEC hydrogels varied as a function of pH on the pK intervals between chitosan (pK = 6.5) and γ‐PGA (pK = 2.27). The isoelectric points (IEP) were shifted to a lower pH with a higher weight ratio of γ‐PGA to chitosan. The elastic modulus was decreased with the weight ratio increasing from 0 : 1 to 1 : 1 (γ‐PGA/chitosan) by ionic crosslinking between the amino groups of chitosan and the carboxyl groups of γ‐PGA. The results of the swelling study showed that the swelling properties of PEC hydrogels were more affected by the change in the elastic restoring force than by the change in the fixed charge concentration depending on the pH. Also, the cytotoxicity of the PEC hydrogels was investigated using normal human dermal fibroblast (NHDF) cell lines, and the results showed the PEC hydrogels were not toxic. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103:386–394, 2007     

Swelling and elasticity of poly (N‐isopropylacrylamide‐co‐4‐vinyl benzene sulfonic acid sodium salt) hydrogels

The mechanical properties and the swelling behavior of hydrogels based on N‐isopropylacrylamide (NIPA) and 4‐vinylbenzenesulfonic acid sodium salt (styrene sulfonate, SSA) monomers were investigated. The mole fraction of SSA in the comonomer feed varied between 0 and 1, whereas the crosslinker ratio was fixed at 1/85. Both the swelling and the elasticity data of the hydrogels swollen in water show that they are in the non‐Gaussian regime. The exponents found for the charge density dependence of the equilibrium swelling ratio as well as for the volume dependence of the gel elastic modulus are in good agreement with the predicted course of the non‐Gaussian elasticity of swollen hydrogels. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 135–141, 2004     

Preparation of pH‐sensitive poly(vinyl alcohol‐g‐methacrylic acid) and poly(vinyl alcohol‐g‐acrylic acid) hydrogels by gamma ray irradiation and their insulin release behavior

A series of pH‐responsive hydrogels were studied as potential drug carriers for the protection of insulin from the acidic environment of the stomach before releasing in the small intestine. Hydrogels based on poly(vinyl alcohol) networks grafted with acrylic acid or methacrylic acid were prepared by a two‐step process. Poly(vinyl alcohol) hydrogels were prepared by gamma ray irradiation (50 kGy) and then followed by grafting either acrylic acid or methacrylic acid onto these poly(vinyl alcohol) hydrogels with subsequent irradiation (5–20 kGy). These graft hydrogels showed pH‐sensitive swelling behavior and were used as carriers for the controlled release of insulin. The in vitro release of insulin was observed for the insulin‐loaded hydrogels in a simulated intestinal fluid (pH 6.8) but not in a simulated gastric fluid (pH 1.2). The release behavior of insulin in vivo in a rat model confirmed the effectiveness of the oral delivery of insulin to control the level of glucose. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 636–643, 2004     

Mechanical properties of poly(N‐isopropyl‐acrylamide‐co‐itaconic acid) hydrogels

Hydrogels of N‐isopropylacrylamide and itaconic acid were synthesized with different monomer ratios and with two crosslinking agent concentrations. The different xerogels were immersed in water and the swelling process was conducted up to equilibrium conditions at two temperatures (22 and 37°C). These temperatures are lower and higher than the transition temperature shown by PNIPA hydrogels. The mechanical properties of the different solvated hydrogels were examined by oscillatory shear measurements at 22 and 37°C. The copolymer volume fraction and the elastic storage modulus of the hydrogels decreased as the itaconic acid percentage in the copolymer increased. This behavior was attributed to the higher hydrophilic character of the itaconic acid comonomer. Effective crosslinking density, molar mass between crosslinks, and the polymer–solvent interaction parameter were determined from the experimental values of the elastic storage moduli and the copolymer volume fractions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2540–2545, 2002     

Preparation and properties of physically crosslinked sodium carboxymethylcellulose/poly(vinyl alcohol) complex hydrogels

A series of physically crosslinked complex hydrogels of poly(vinyl alcohol) (PVA) and sodium carboxymethylcellulose (CMC) were prepared via physical mixing and a freeze/thaw technique. The morphology of the CMC/PVA complex gels was analyzed with differential scanning calorimetry and wide‐angle X‐ray diffraction. It was found that the crystallinity and melting temperature of the complex gels decreased, whereas the glass‐transition temperature increased, with an increase in the content of CMC. The reswelling of the complex gels was pH‐responsive and relied on the content of CMC and the freeze/thaw cycles. A network structure model of the complex gel was presented. PVA crystalline regions served as physical crosslinks; the interaction between CMC and PVA resulted in intramolecular entanglements. It was also found that the model drug hemoglobin was released completely from the complex hydrogels in 4 h, and its release rate increased with an increase in the content of CMC. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis,characterization, and in vitro drug release study of 3‐arm poly‐β‐alanine

Synthesis of three arms star‐shaped poly‐β‐alanine (3‐b‐ala) based on tri(prop‐2‐yn‐1‐yl) benzene‐1,3,5‐tricarboxylate (TBT) and azido terminated poly‐β‐alanine (N₃‐P‐ala) was performed using click reaction. TBT was synthesized by nucleophilic substitution reaction between propargyl alcohol and 1,3,5‐benzenetricarbonyltrichloride. For the first time, N₃‐P‐ala was synthesized through anionic polymerization of acrylamide using sodium azide as an initiator. TBT was characterized by FT‐IR and ¹HNMR. N₃‐p‐ala was characterized by FT‐IR, GPC, and ¹HNMR and 3‐b‐ala was characterized by FT‐IR, GPC, ¹HNMR, TGA, and XRD. The synthesized 3‐b‐ala was used for drug loading and releasing studies. Polymer loaded drug (3‐b‐ala‐D) hybrid was used in in vitro studies of drug (Diclofenac sodium) release in phosphate buffer solution (PBS) at 37 ± 0.5°C and pH 7.4. The drug loading and releasing studies were analyzed by UV‐visible spectrophotometer. 3‐b‐ala‐D was examined by AFM to analyze the surface morphology and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42124.     

Swelling behavior and cell viability of dehydrothermally crosslinked poly(vinyl alcohol) hydrogel grafted with N‐vinyl pyrrolidone or acrylic acid using γ‐radiation

To improve equilibrium water content, dehydrothermally crosslinked poly(vinyl alcohol) (PVA) hydrogel was grafted with N‐vinyl pyrrolidone (NVP) or acrylic acid (AA) monomer using γ‐radiation. Swelling behavior of the grafted hydrogels was studied in phosphate‐buffered saline, and cell viability was evaluated using fibroblast cells from mouse connective tissue. Equilibrium water content of AA‐ and NVP‐grafted PVA hydrogel ranged between 40–60% and 60–80%, respectively, depending on radiation dose and monomer concentration. For maximum degree of swelling, the optimum monomer concentration and radiation dose were 20% by weight and 20 kGy, respectively. Fibroblast cells seeded on NVP‐grafted hydrogel had an extended oval morphology while those seeded on AA‐grafted PVA had a rounded spherical morphology. These results support the use of NVP for grafting PVA to increase swelling and improve cell viability. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2862–2868, 2004     

Preparation of poly(vinyl amine)‐grafted crosslinked poly(vinyl alcohol) microspheres

Crosslinked poly(vinyl alcohol) (CPVA) microspheres were first prepared via the suspension polymerization of vinyl acetate and the alcoholysis of poly(vinyl acetate). Afterwards, a two‐step method involving graft polymerization and Hofmann degradation was used to prepare functional poly(vinyl amine)‐grafted crosslinked poly(vinyl alcohol) (PVAm–CPVA) microspheres, onto which poly(vinyl amine) (PVAm) macromolecules were grafted. The graft polymerization of acrylamide (AM) on CPVA microspheres was performed with cerium salt as the initiator in an acidic aqueous medium, resulting in polyacrylamide (PAM)‐grafted CPVA microspheres. Subsequently, the grafted PAM was transformed into PVAm via the Hofmann degradation reaction, and PVAm–CPVA microspheres were prepared. The effects of the main factors on the graft polymerization and Hofmann degradation were examined, and the reaction mechanisms were researched in depth. The experimental results showed that for the graft polymerization of AM on CPVA microspheres initiated by cerium salt, the acid concentration and the amount of cerium salt affected the grafting degree of PAM greatly. For the Hofmann degradation reaction of the grafted PAM, the amination degree of PVAm–CPVA microspheres was obviously affected by the amount of sodium hypochlorite in the presence of sodium hydroxide. The preliminary adsorption tests showed that PVAm–CPVA microspheres were multifunctional and had strong adsorption ability for Fe(III) ions by chelation action and for chromate ions (CrO) by strong electrostatic interactions. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and characterization of novel pH‐responsive poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) hydrogels for drug delivery

In this study, N‐allylsuccinamic acid (NASA) was synthesized in a single step with a yield of 85%. Carboxylic acid containing NASA was characterized through Fourier transform infrared (FTIR) radiation and ¹H‐NMR and ¹³C‐NMR analysis, and then it was used for synthesis of poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) [p(HEMA‐co‐NASA)] hydrogels. The structure of the obtained pH‐responsive p(HEMA‐co‐NASA) hydrogels were characterized with FTIR spectroscopy and scanning electron microscopy analysis, and their swelling characterization was carried out under different drug‐release conditions. In the application step of the study, the hydrogels were used for the in vitro release of vitamin B12 and Rhodamine 6G, which were selected as model drugs. We determined that the hydrogels used as a drug‐delivery matrix could release the drug they had absorbed under different release conditions (phosphate‐buffered saline, 0.9% NaCl, and pH 1.2) at high rates for time periods of up to 24 h. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39660.     

Preparation of poly(acrylic acid)–chitosan hydrogels by gamma irradiation and in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) (AAc) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a gamma irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid content increased. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when the 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30‐kGy radiation dose. Also, an increase of swelling degree with an increase in the pH was noticed and showed the highest value at pH 12. The drug, 5‐fluorouracil, was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at the intestinal pH and the rest of the drug had been released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3660–3667, 2003     

Soluble and crosslinked hydrophilic films based on compositions of poly(acrylic acid) and poly(2‐hydroxyethyl vinyl ether) for controlled drug release

Soluble and crosslinked films based on compositions of poly(acrylic acid) and poly(2‐hydroxyethyl vinyl ether) were prepared. Solubility, morphology, mechanical characteristics, and swelling properties of the films were investigated. Potential applications of the polymer complex films in controlled drug delivery were also examined. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 137–142, 2003     

Novel physical hydrogels composed of opened‐ring poly(vinyl pyrrolidone) and chitosan derivatives: Preparation and characterization

A novel, physically stabilized hydrogel system composed of chitosan (Chi) or its derivatives [e.g., carboxymethyl chitosan (CMC), sodium carboxymethyl chitosan, or trimethyl carboxymethyl chitosan (TMCMC)] with poly(vinyl pyrrolidone) (PVP) or opened‐ring poly(vinyl pyrrolidone) (OR–PVP) were prepared and characterized. TMCMC was synthesized by a novel method with dimethylsulfate as the methylation agent. The synthesized materials were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, ¹³C‐NMR, and size exclusion chromatography. The mechanical properties, gel fraction, swelling behavior, and water state of the prepared hydrogels were investigated. Gelation occurred when the OR–PVP and Chi solutions were blended within a few seconds. However, the gelation of the OR–PVP and CMC solutions needed pH adjustment. No gelation occurred when the solutions of TMCMC and PVP or OR–PVP were blended. The quaternization or protonization of  NH₂ groups may have prevented the gelation of the solutions. The amino groups of Chi derivatives should have been free to take part in hydrophilic bonds between the two polymers. The physical entanglement of polymeric chains and strong hydrogen bonds between the polymers were considered as mechanisms for the formation of the physical hydrogels. The physical hydrogels showed ionic and pH‐sensitive swelling properties. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Electroactive characteristics of interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and poly(N‐isopropylacrylamide)

An interpenetrating polymer network (IPN) composed of poly(vinyl alcohol) (PVA) and poly(N‐isopropylacrylamide) (PNIPAAm) was prepared by the sequential IPN method. The equilibrium swelling ratio and bending behavior under electric fields of the IPN hydrogel were measured in an aqueous NaCl solution. The IPN exhibited a high equilibrium swelling ratio, in the range 280–380%. When the IPN in aqueous NaCl solution was subjected to an electric field, the IPN showed significant and quick bending toward the cathode. The IPN hydrogel also showed stepwise bending behavior, depending on the electric stimulus. In addition, the ionic conductivity of the IPN hydrogel was measured using dielectric analysis, and its conductive behavior followed the Arrhenius equation. The conductivity of the IPN hydrogel and the activation energy for the form of the IPN were 1.68 × 10^?5 S/cm at 36°C and 61.0 kJ/mol, respectively. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 890–894, 2003     

Swelling behavior of semi‐interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and poly(acrylamide‐co‐sodium methacrylate)

Interpenetrating polymer network (IPN) hydrogels based on poly(vinyl alcohol) (PVA) and poly(acrylamide‐co‐sodium methacrylate) poly(AAm‐co‐SMA) were prepared by the semi IPN method. These IPN hydrogels were prepared by polymerizing aqueous solution of acrylamide and sodium methacrylate, using ammonium persulphate/N,N,N¹,N¹‐tetramethylethylenediamine (APS/TMEDA) initiating system and N,N¹‐methylene‐bisacrylamide (MBA) as a crosslinker in the presence of a host polymer, poly(vinyl alcohol). The influence of reaction conditions, such as the concentration of PVA, sodium methacrylate, crosslinker, initiator, and reaction temperature, on the swelling behavior of these IPNs was investigated in detail. The results showed that the IPN hydrogels exhibited different swelling behavior as the reaction conditions varied. To verify the structural difference in the IPN hydrogels, scanning electron microscopy (SEM) was used to identify the morphological changes in the IPN as the concentration of crosslinker varied. In addition to MBA, two other crosslinkers were also employed in the preparation of IPNs to illustrate the difference in their swelling phenomena. The swelling kinetics, equilibrium water content, and water transport mechanism of all the IPN hydrogels were investigated. IPN hydrogels being ionic in nature, the swelling behavior was significantly affected by environmental conditions, such as temperature, ionic strength, and pH of the swelling medium. Further, their swelling behavior was also examined in different physiological bio‐fluids. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 302–314, 2005