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     

In vitro release of salicylic acid through poly(vinyl alcohol‐g‐itaconic acid) membranes

In this study, itaconic acid (IA) was grafted on poly(vinyl alcohol) (PVA) at two different grafting percentages, 7.0% (w/w) and 14.0% (w/w), and membranes were prepared from the grafted copolymer (PVA‐g‐IA). Performances of PVA and PVA‐g‐IA membranes for the transdermal release of salicylic acid (SA) at in vitro conditions were investigated by using 2.0 mg/mL SA solutions. Effect of the pH on the release of SA was studied by keeping pH of donor and acceptor solutions in a range of (2.1–7.4). Permeation studies were also carried on at different SA concentrations. Effect of temperature on the release of SA was investigated in the temperature range of (32–39) (±1)°C. Results showed that presence of IA decreased the release of SA from the PVA membranes and 73% SA was released at the end of 48 h at (32 ± 1)°C from the IA‐1 membranes. pH affected the release of SA through the grafted membranes and studies showed that release of SA was high with donor solution pH of 2.1. When the pH of donor and receiver solutions were kept at the same pH value, the overall SA% in permeate increased. Increase in concentration of SA decreased the release of SA for the studied membranes. Release of SA from PVA‐g‐IA membranes was temperature sensitive and increase in temperature from (32 ± 1)°C to (39 ± 1)°C increased the release percentage of SA by 24% (w/w). The overall activation energy for the permeation of SA through IA‐1 membrane was found to be 22.97 kJ/mol. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

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     

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     

Release of salicylic acid through poly(vinyl alcohol)/poly(vinyl pyrrolidone) and poly(vinyl alcohol‐g‐N‐vinyl‐2‐pyrrolidone) membranes

A controlled release profile of salicylic acid (SA) for transdermal administration has been developed. Poly (vinyl alcohol) (PVA) and Poly(vinyl alcohol)/Poly(vinyl pyrrolidone) (PVP) blended preparations were used to prepare the membranes by solvent‐casting technique. The release of the drug from the membranes was evaluated at in vitro conditions. The effects of PVA/PVP (v/v) ratio, pH, SA concentration and temperature were investigated. 60/40 (v/v) PVA/PVP ratio was found to be the best ratio for the SA release. Increase in pH and temperature was observed to increase the transport of SA. Instead of blending PVA with PVP, N‐Vinyl‐2‐pyrrolidone (VP) was grafted onto the PVA and the delivery performance for SA was compared with that of the blended PVA/PVP membranes. Grafted membranes gave higher transport percentages than the blended membranes. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:1244–1253, 2006     

Dually responsive multinetworked hydrogels with improved performances by covalently bonding poly(N‐isopropylacrylamide)‐based microgels and poly(vinyl alcohol) skeleton

To prepare intelligent hydrogels with both good mechanical performance and fast response, a series of multinetworked composite hydrogels with pH and thermo‐responsivity were designed and fabricated combining the advantages of both interpenetrating polymer network hydrogels and microgels. To begin with, precipitation polymerization of N‐isopropylacrylamide, methacrylic acid and polyethyleneglycol methacrylate was carried out in poly(vinyl alcohol) (PVA) aqueous solution, yielding thermo‐ and pH‐responsive copolymeric microgels. Then glutaraldehyde was added to the obtained microgel dispersion to covalently bond the microgel particles and PVA through acetal reaction, leading to the formation of multinetworked hydrogels with dual responses. The morphology of microgels and the internal microstructure of composite hydrogels were characterized by transmission electron microscope and scanning electron microscope, respectively. The influence of the PVA content and glutaraldehyde dosage on the mechanical behavior of the prepared hydrogels was investigated by means of uniaxial compressive tests. Experimental results reveal that the as‐prepared composite hydrogels exhibit enhanced mechanical performance compared to conventional hydrogels. Investigation onthe swelling and deswelling behaviors shows that they possess good temperature‐ and pH‐sensitivity andswell/deswell more rapidly than conventional hydrogels. POLYM. COMPOS., 2012. © 2013 Society of Plastics Engineers     

pH‐ and temperature‐sensitive in vitro release of salicylic acid through poly(vinyl alcohol‐g‐acrylamide) membranes

In this study, acrylamide (AAm) was grafted onto poly(vinyl alcohol) (PVA) in solution with UV radiation, and membranes were prepared from the graft copolymer (PVA‐g‐AAm) for transdermal release of salicylic acid (SA) at in vitro conditions. Permeation studies were carried out using a Franz‐type diffusion cell. Release characteristics of SA through PVA and PVA‐g‐AAm membranes were studied using 2.0 mg/mL SA solutions. Effects of the presence of AAm in the copolymer, pH of donor and acceptor solution, and concentration of SA and temperature on the release of SA were investigated. Permeation of SA through the membranes was found to be pH‐dependent, and increase in pH generally increased the release percentage of SA, and the presence of AAm in the membrane positively affected the permeation. The effect of concentrations of SA on the permeation was also searched using saturated solution of SA, and permeated amount of SA was found to be less than in the case of unsaturated SA solution. Studies showed that the release of SA from PVA‐g‐AAm membranes was temperature‐sensitive and increase in temperature increased the permeation rate. 82.76% (w/w) SA was released at the end of 24 h at (39 ± 1)°C, and the overall activation energy for the permeation of SA through PVA‐g‐AAm membranes was found to be 19.65 kJ/mol. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

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 dual responsive sodium alginate‐g‐poly(vinyl alcohol) hydrogel

Poly(vinyl alcohol) (PVA) was chosen as a controllable gelator to prepare sodium alginate (SA)‐based physically cross‐linked dual‐responsive hydrogel by three steps. First, polyvinyl acetate (PVAc) was grafted onto SA via radical copolymerization. Then, the copolymer was subsequently converted into SA‐g‐poly(vinyl alcohol) (SAPVA) by alcoholysis reaction. PVA content of SAPVA was tailored by controlling the graft percentage of PVAc, i.e. through varying the amount of vinyl acetate during copolymerization. Finally, SAPVA hydrogels were formed by freezing‐thawing cycles. The structure of the graft copolymers was verified with FTIR spectroscopy. X‐ray diffraction analysis results revealed that the crystallinity of SAPVA hydrogels depended on the PVA content of SAPVA. The swelling test showed that SAPVA hydrogels were pH‐responsive, and the swelling was reversible. SAPVA hydrogels also behaved electric‐responsive. In addition, the pH‐sensitivity of SAPVA hydrogels was able to be controlled with the composition of the hydrogels. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Medicated wound dressings based on poly(vinyl alcohol)/poly(N‐vinyl pyrrolidone)/chitosan hydrogels

Poly(vinyl alcohol)/poly(N‐vinyl pyrrolidone) (PVP)/chitosan hydrogels were prepared by a low‐temperature treatment and subsequent ⁶⁰Co γ‐ray irradiation and then were medicated with ciprofloxacin lactate (an antibiotic) and chitosan oligomer (molecular weight = 3000 g/mol). The gel content, swelling ratio, tensile strength, and crystallinity of the hydrogels were determined. The effects of the chitosan molecular weight, the low‐temperature treatment procedure, and the radiation dosage on the hydrogel properties were examined. The molecular weight of chitosan was lowered by the irradiation, but its basic polysaccharide structure was not destroyed. Repeating the low‐temperature treatment and γ‐ray irradiation caused effective physical crosslinking and chemical crosslinking, respectively, and contributed to the mechanical strength of the final hydrogels. The incorporation of PVP and chitosan resulted in a significant improvement in the equilibrium swelling ratio and elongation ratio of the prepared hydrogels. The ciprofloxacin lactate and chitosan oligomer were soaked into the hydrogels. Their in vitro release behaviors were examined, and they were found to follow diffusion‐controlled kinetics. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2453–2463, 2006     

Synthesis and characterization of an interpenetrating polymer network composed of poly(methacrylic acid) and poly(vinyl alcohol)

Temperature and pH‐responsive interpenetrating polymer network (IPN) hydrogels, constructed with poly(methacrylic acid) (PMAA) and poly(vinyl alcohol) (PVA), by a sequential IPN method, were studied. The characterization of IPN hydrogels was investigated by Fourier‐transform infrared spectroscopy, differential scanning calorimetry (DSC) and swelling under various conditions. The IPN hydrogels exhibited relatively high swelling ratios, in the range 230–380 %, at 25 °C. The swelling ratios of the PMAA/PVA IPN hydrogels were pH and temperature dependent. DSC was used for the quantitative determination of the amounts of freezing and non‐freezing water. The amount of free water increased with increasing PMAA content in the IPN hydrogels. Copyright © 2004 Society of Chemical Industry     

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     

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     

Preparation of poly(vinyl alcohol)/poly(acrylic acid) microcapsules and microspheres and their pH-responsive release behavior

The pH-responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogel microparticles containing vitamin B₁₂ were prepared with emulsion polymerization. Both microcapsule and microsphere were easily produced by simply changing the sequence of ingredient addition during the emulsion polymerization. The microparticles showed the faster and larger release of vitamin B₁₂ due to the higher swelling of hydrogel by electrostatic repulsion of carboxylate groups in poly(acrylic acid) as the pH was changed into more basic condition. The microcapsules showed a faster release than the microspheres did due to the less hindered passage through the thinner shell of microcapsules. The poly(vinyl alcohol)/poly(acrylic acid) hydrogel microparticles either protected or released the vitamin B₁₂ effectively depending on pH.     

Physicochemical characterization of hydrogels based on polyvinyl alcohol–vinyl acetate blends

Hydrogels made of polyvinyl alcohol–vinyl acetate and its blends with water soluble polymer were studied in terms of swelling behavior, microstructure, and dynamic mechanical properties. Hydrogels prepared by blending polyvinyl alcohol–vinyl acetate with either polyacrylic acid or poly(4‐vinyl pyridine) exhibited a strong pH dependency. When poly(vinyl pyrrolidone) was used for blending, an unusual pH dependency was observed. An increase in the equilibrium water content in all systems resulted in an increase in the freezable water as determined by DSC. Critical point drying led to a striated surface on polyacrylic acid–polyvinyl alcohol–vinyl acetate hydrogels, whereas a porous structure was observed on the freeze‐dried poly(vinyl pyrrolidone)–polyvinyl alcohol–vinyl acetate gels. Hydrogels with elevated storage modulus were obtained when either polyvinyl alcohol–vinyl acetate alone or polyacrylic acid–polyvinyl alcohol–vinyl acetate blends were thermally treated at high temperatures (i.e., 150°C). Low storage modulus was observed for both poly(vinyl pyrrolidone) and poly(4‐vinyl pyridine)‐containing hydrogels. Temperature dependency of storage modulus from 20 to 60°C was observed only for poly(4‐vinyl pyridine)–polyvinyl alcohol–vinyl acetate hydrogels. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 3578–3590, 2001     

Hydrolyzed collagen‐grafted‐poly[(acrylic acid)‐co‐(methacrylic acid)] hydrogel for drug delivery

Hydrolyzed collagen‐grafted‐poly[(acrylic acid)‐co‐(methacrylic acid)] hydrogels were synthesized by solution polymerization and confirmed by infrared spectroscopy. From sequential univariate analysis, the optimal molar ratio of acrylic acid: methacrylic acid was 92:8 in the presence of N,N′‐methylenebisacrylamide, ammonium persulfate, and N,N,N′,N′‐tetramethylethylenediamine at 0.12, 0.015, and 0.2% mol of the monomers, respectively. The water absorbency of this hydrogel was both pH‐ and temperature‐dependent, but was higher in nonbuffered water than in boric acid/citric acid/phosphate buffer under the same conditions. The optimal hydrogel could swiftly swell and deswell in neutral and acid solutions, respectively. Its potential application in drug delivery was examined using insulin and methylene blue as model payload drugs. Loading in a 50% (v v^?1) ethanol solution gave a higher insulin loading level than in the buffer water. Insulin and methylene blue were both released at pH 6.8 but not at pH 1.2, but followed first order kinetics and the Higuchi equation, respectively. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45654.     

Thermally crosslinked anionic hydrogels composed of poly(vinyl alcohol) and poly(γ‐glutamic acid): Preparation,characterization, and drug permeation behavior

pH‐sensitive anionic hydrogels composed of poly(vinyl alcohol) (PVA) and poly(γ‐glutamic acid) (γ‐PGA) were prepared by the freeze drying method and thermally crosslinked to suppress hydrogel deformation in water. The physical properties, swelling, and drug‐diffusion behaviors were characterized for the hydrogels. In the equilibrium swelling study, PVA/γ‐PGA hydrogels shrunk in pH regions below the pK_a (2.27) of γ‐PGA, whereas they swelled above the pK_a. In the drug‐diffusion study, the drug permeation rates of the PVA/γ‐PGA hydrogels were directly proportional to their swelling behaviors. The cytocompatibility test showed no cytotoxicity of the PVA/γ‐PGA hydrogels for the 3T3 fibroblast cell lines. The results of these studies suggest that hydrogels prepared from PVA and γ‐PGA could be used as orally administrable drug‐delivery systems. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Photo/pH dual‐responsive biocompatible poly(methacrylic acid)‐based particles for triggered drug delivery

A novel dual‐responsive (light and pH) particle based on poly(methacrylic acid), poly(methacrylic acid)–poly[1‐(2‐nitrophenyl)ethane‐1,2‐diyl bis(2‐methylacrylate)]was prepared with the facile method of two‐step homogeneous radical polymerization with methacrylic acid as the monomer and 1‐(2‐nitrophenyl)ethane‐1,2‐diyl bis(2‐methylacrylate) as a photodegradable crosslinker. Photolytic assessments were conducted upon irradiation with a UV lamp; this led to particle disintegration caused by cleavage of the photolabile crosslinking points. The light‐dependent degradation was investigated through particle size changes, absorption spectra variations, surface morphology changes, Fourier transform infrared spectroscopy, and the release of Nile red from the particles after irradiation. The pH dependence of the particle systems induced by the protonation and deprotonation of poly(methacrylic acid) was also confirmed by fluorescence spectroscopy. The triggered release of fluorescein diacetate was investigated to demonstrate that the release behavior in cells was light dependent. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44003.     

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     

Uses of electron‐beam irradiation to prepare pH‐ and temperature‐sensitive hydrogels from reactive poly(vinyl alcohol) grafts

Thermosensitive poly(vinyl alcohol)‐graft‐(maleic anhydride), PVA‐MA, and poly(vinyl alcohol)‐graft‐(N‐isopropylacrylamide maleic anhydride) (PVA‐MA‐NIPAAm) copolymers containing carboxyl groups were prepared using electron beam irradiation at dose 80 kGy. The swelling ratios of the cross‐linked gels were measured at various temperatures. The LCST values were measured using DSC technique. The temperature dependence of the swelling ratios of the cross‐linked copolymers and terpolymers were measured at different temperatures. The swelling ratios of copolymers increased with increasing temperature up to 25–38°C, then decreased. The swelling behavior of both copolymers and terpolymers was referred to formation of hydrogen bonds between amide group of NIPAAm moieties and carboxyl group in MA moieties and to hydrophobic interaction due to methyl groups of NIPAAm. The swelling behaviors of these gels were analyzed in buffer solution at various pH. Swelling ratios of all gels were relatively high and they showed reasonable sensitive to pH. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008