Multifunctional gentamicin supplementation of poly(γ‐glutamic acid)‐based hydrogels for wound dressing application

The process of wound healing is composed of coagulation, inflammation, fibroplasia, collagenation, epithelization, and wound contraction. The wound dressing should protect the wound from bacterial infection, maintain a moist healing environment, and promote cell migration to reconstruct damaged tissue, and be easy to apply and remove to improve patient comfort. The purpose of our study was to develop multifunctional hydrogels composed of genipin‐crosslinked biodegradable biomaterials of poly(γ‐glutamic acid) and gelatin, encapsulating gentamicin to accelerate wound healing. The results of swelling ratio measurements clearly indicate that hydrogel composition of poly(γ‐glutamic acid)–gelatin had a higher swelling ratio and lower peel adhesion properties than gelatin hydrogel alone. In an in vitro study, the gentamicin incorporated in prepared hydrogels effectively inhibited target microorganisms and produced a higher expression of Type I collagen in fibroblast cells. Confocal laser scanning microscopy revealed that the fibroblast cells cultured in the hydrogel membranes produced fibroblast cell migration and showed a continuous lined cytoskeletal distributing status. In the in vivo study, it was found that the gentamicin incorporated in genipin‐crosslinked γ‐PGA–gelatin wound dressing demonstrates the potential of such biologically functionalized dressing to accelerate wound closure and, hence, its potential clinical usefulness. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

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     

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     

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     

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     

In situ injectable poly(γ‐glutamic acid) based biohydrogel formed by enzymatic crosslinking

Enzymatic crosslinking was developed to prepare in situ forming poly(γ‐glutamic acid) (γ‐PGA) based hydrogel in this study. First, the precursor of poly(γ‐glutamic acid)–tyramine (γ‐PGA–Ty) was synthesized through the reaction of carboxyl groups from a γ‐PGA backbone with tyramine. The structure of the grafted precursor was confirmed by ¹H‐NMR and Fourier transform infrared spectroscopy. After that, the crosslinking of the phenol‐containing γ‐PGA–Ty precursor was triggered by horseradish peroxidase in the presence of H₂O₂; this resulted in the formation of the γ‐PGA–Ty hydrogels. The equilibrium water content, morphology, enzymatic degradation rate, and mechanical properties of the hydrogels were characterized in detail. The data revealed that the well‐interconnected hydrogels had tunable water contents, mechanical properties, and degradability through adjustments of the composition. Furthermore, cell experiments proved the biocompatibility of the hydrogels by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. These characteristics provide an opportunity for the in situ formation of injectable biohydrogels as potential candidates in cell encapsulation and drug delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42301.     

A poly(γ‐glutamic acid)‐based hydrogel loaded with superoxide dismutase for wound healing

The purpose of this study was to develop a poly(γ‐glutamic acid) (γ‐PGA)‐based hydrogel loaded with superoxide dismutase (SOD) to accelerate wound healing. First, γ‐PGA was modified with taurine (γ‐PGAS), and then the SOD‐loaded γ‐PGAS/γ‐PGA hydrogel (SOD‐PGAS/PGA‐H) was prepared by cross‐linking of ethylene glycol diglycidyl ether. The swelling behavior and water vapor transmission rate revealed that PGAS/PGA‐H could create a moist environment for wound surface. In vitro kinetics of SOD release showed that SOD released from PGAS/PGA‐H maintained high activity and SOD‐PGAS/PGA‐H effectively scavenged the superoxide anion. The results of our fibroblast proliferation experiments showed that PGAS/PGA‐H had good cytocompatibility. The effects of SOD‐PGAS/PGA‐H on wound healing were examined in a Type I diabetic rat model with full‐thickness wounds. Twenty‐one days after grafted to wounds, SOD‐PGAS/PGA‐H exhibited a higher rate of wound healing than control group and showed increased collagen deposition and epithelialization. SOD‐PGAS/PGA‐H seems to promote better wound healing and thus might be a promising candidate for wound healing management. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42033.     

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     

Modification via preparation for poly(3‐hydroxybutyrate) films: Water‐transport phenomena and sorption

The effect of the preparation technique on the sorption–diffusion parameters of poly(3‐hydroxybutyrate) (PHB) films was studied. The films formed by a single‐stage technique have an axial texture of the crystalline phase, with the polymer chain oriented predominantly perpendicularly to the film plane. Moreover, the crystallites in PHB are preferably ordered in stacks in the course of diffusion; the alignment of the crystallites noticeably decreases the “sites” of PHB (polar groups) which are accessible to water molecules. As a result, the sorption capacity decreases but the rate of diffusion increases. On the contrary, PHB films prepared by a two‐stage technique are characterized by a poor ordering of crystallites without texture organization. Here, the sorption/immobilization on the polar groups of PHB is increased, but diffusivities are decreased. Concentration dependencies of the water‐diffusion coefficient are discussed. Additional information on the existence of protein impurities in the PHB samples obtained by the above two preparation techniques was obtained by FTIR spectroscopy and H–D exchange methods. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 475–480, 2000     

Transesterification in homogeneous poly(ε‐caprolactone)–epoxy blends

Transesterification has been investigated in poly(ε‐caprolactone) (PCL)–epoxy blends. In the hot melt process, the hydroxyl on diglycidyl ether of bisphenol‐A (DGEBA) monomers is too low to give a noticeable transesterification reaction. In the postcure process, model reactions reveal that the hydroxyls from a ring‐opening reaction are able to react with the esters of PCL. In the meantime, the PCL molecular weight decrease and its distribution becomes broader. Nuclear magnetic resonance spectra reveal that fraction of the tertiary hydroxyls converts to secondary hydroxyls. In the cured DGEBA–3,3′‐dimethylmethylene‐di(cyclohexylamine)–PCL blend, a homogeneous morphology is achieved. PCL segments are grafted onto the epoxy network after postcuring and result in the lower T_g observed in the differential scanning calorimetry thermogram. A higher transesterification extent also results in broader transition peaks by dynamic mechanical analysis. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 75–82, 1999     

Thermal and rheological properties of poly(vinyl alcohol) and water‐soluble chitosan hydrogels prepared by a combination of γ‐ray irradiation and freeze thawing

Poly(vinyl alcohol) (PVA)/water‐soluble chitosan (ws‐chitosan) hydrogels were prepared by a combination of γ‐irradiation and freeze thawing. The thermal and rheological properties of these hydrogels were compared with those of hydrogels prepared by pure irradiation and pure freeze thawing. Irradiation reduced the crystallinity of PVA, whereas freeze thawing increased it. Hydrogels made by freeze thawing followed by irradiation had higher degrees of crystallinity and higher melting temperatures than those made by irradiation followed by freeze thawing. ws‐Chitosan disrupted the ordered association of PVA molecules and decreased the thermal stability of both physical blends and hydrogels. All the hydrogels showed shear‐thinning behavior in the frequency range of 0.2–100 rad/s. Hydrogels made by freeze thawing dissolved into sol solutions at about 80°C, whereas those made by irradiation showed no temperature dependence up to 100°C. The chemical crosslinking density of the hydrogels made by irradiation followed by freeze thawing was much greater than that of hydrogels made by freeze thawing followed by irradiation. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Transesterification reaction kinetics of poly(ethylene terephthalate/poly(ethylene 2,6‐naphthalate) blends

The transesterification reaction of poly(ethylene terephthalate)/poly(ethylene 2,6‐naphthalate) blends during melt‐mixing was studied as a function of blending temperature, blending time, blend composition, processing equipment, and different grades of poly(ethylene terephthalate) and poly(ethylene 2,6‐naphthalate). Results show that the major factors controlling the reaction are the temperature and time of blending. Efficiency of mixing also plays an important role in transesterification. The reaction kinetics can be modeled using a second‐order direct ester–ester interchange reaction. The rate constant (k) was found to have a minimum value at an intermediate PEN content and the activation energy of the rate constant was calculated to be 140 kJ/mol. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2422–2436, 2001     

Preparation and microstructural analysis of poly(ethylene oxide) comb‐type grafted poly(N‐isopropyl acrylamide) hydrogels crosslinked by poly(ϵ‐caprolactone)

Poly(N‐isopropyl acrylamide) (PNIPAAm)‐graft‐poly(ethylene oxide) (PEO) hydrogels crosslinked by poly(?‐caprolactone) diacrylate were prepared, and their microstructures were investigated. The swelling/deswelling kinetics and compression strength were measured. The relationship between the structure and properties of hydrogel are discussed. It was found that the PEO comb‐type grafted structure reduced the thermosensitivity and increased the compression strength. The addition of poly(?‐caprolactone) (PCL) accelerated the deswelling rate of the hydrogels. Meanwhile, the entanglement of PCL chains restrained the further swelling of the network of gels. The PCL crosslinking agent and PEO comb‐type grafted structure made the behavior of the hydrogels deviate from the rubber elasticity equations. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Polymeric calcium phosphate cements incorporated with poly‐γ‐glutamic acid: Comparative study of poly‐γ‐glutamic acid and citric acid

Polymeric calcium phosphate cements (PCPC) derived from biodegradable poly‐γ‐glutamic acid (γ‐PGA) were prepared in an attempt to improve the mechanical strength of calcium phosphate cement (CPC). The characteristics of the PCPCs were compared with those of cement incorporated with citric acid. The diametral tensile and compressive strengths of the CPC incorporated with γ‐PGA were significantly higher than that of cement incorporated with citric acid at equivalent concentrations (P < 0.05). The maximal diametral tensile and compressive strengths of the CPC incubated for 1 week in physiological saline solution were approximately 18.0 and 50.0 MPa, respectively. However, the initial setting time of the PCPC was slower than that of CPC incorporated with citric acid. The formation of ionic complexes between calcium ions and γ‐PGA was observed using FTIR spectroscopy. Hydroxyapatite (HA) formation was retarded by γ‐PGA incorporation according to scanning electronic microscopy (SEM) and powder X‐ray diffraction (XRD) observations. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Water transport properties in poly(3‐hydroxybutyrate) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) biopolymers

Water sorption and diffusion have been investigated in poly(3‐hydroxybutyrate) (PHB) and three poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) copolymers [P(HB‐HV)] by means of a Cahn electromicrobalance. Permeability of these samples have been determined using a gravimetric permeation cell. Two experimental setups were used for the gravimetric sorption measurements, under dynamic and static conditions, respectively. The differences observed in the results obtained using these techniques are discussed. The sorption measurements have evidenced the tendency of water molecules to form aggregates or clusters in the polymer. In addition, the static sorption method revealed the potential of PHB and P(HB‐HV) to undergo molecular relaxations, eventually leading to a partial desorption of the previously sorbed water after an induction period. The clustering effect was adequately described by the polycondensation model. On the other hand, the interpretation of the diffusivity in terms of mobility coefficients has revealed a competition between a plasticization effect and clustering. As a whole, water transport properties in PHB and its copolymers can be considered to be very close in magnitude to those of common thermoplastics such as PVC and PET. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 455–468, 1999     

Isothermal kinetics of (E)‐4‐(4‐metoxyphenyl)‐4‐oxo‐2‐butenoic acid release from a poly(acrylic acid‐co‐methacrylic acid) hydrogel

A kinetic study of the release of the drug (E)‐4‐(4‐metoxyphenyl)‐4‐oxo‐2‐butenoic acid (MEPBA) from a poly(acrylic acid‐co‐methacrylic acid) (PAA‐co‐MA) hydrogel was performed. The isothermal kinetic curves of MEPBA release from the PAA‐co‐MA hydrogel in bidistilled water at different temperatures ranging from 20 to 40°C were determined. The reaction rate constants of the investigated process were determined with the initial rate, the saturation rate, and Peppas's semiempirical equation. Also, a model‐fitting method for the determination of the kinetics model of drug release was applied. The influence of α at the values of the kinetic parameters and the presence of a compensation effect was established. A procedure for the determination of the distribution function of the activation energies was developed. This procedure was based on the experimentally determined relationship between the activation energy and α. The mechanism of active compound release is discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Addition of α‐tocopherol on poly(lactic acid): Thermal,mechanical, and sorption properties

This work investigates the effect of the addition of a well‐known antioxidant, α‐tocopherol in poly (lactic acid) flexural and barrier properties. For that purpose, films of poly(lactic acid) enriched with 0, 2.2, and 4.4% of α‐tocopherol were prepared. Differential scanning calorimetry, thermogravimetric analysis, and dynamic mechanical analysis were used to characterize the changes in the mechanical and thermal properties. The sorption of oxygen and carbon dioxide in the prepared enriched films of poly(lactic acid) was measured at different temperatures between 283 and 313 K and pressures up to atmospheric pressure using a Quartz Crystal Microbalance. Although no significant changes were found in the mechanical and thermal properties, the addition of α‐tocopherol promotes an increasing in the oxygen sorption and the convex shape of the isotherms indicate a strong interaction gas‐polymer. Regarding the sorption of carbon dioxide, no pronounced effect was found. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Characterization of poly(N‐(hydroxymethyl)methacrylamide‐ATU) hydrogels synthesized by γ radiation

Poly(N‐(hydroxymethyl)methacrylamide‐1‐allyl‐2‐thiourea), (poly(NHMMA‐ATU)) hydrogels were synthesized by γ radiation, using ⁶⁰Co γ source at different radiation doses, to change the porosity and crosslinking density of the hydrogels. The percent of 1‐allyl‐2‐thiourea (ATU) in the monomer mixture before the irradiation was varied between 2.5% and 10.0%, to increase the content of ATU, which was involved in some different applications in the hydrogels. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), elemental analysis, and the swelling experiments were used to characterize the poly(NHMMA‐ATU) hydrogels synthesized in this study. Characterization results of hydrogels showed that crosslinking density of the hydrogels was increased by the increasing radiation dose and ATU content in the irradiated mixture. Swellability of these hydrogels was found to be high enough to allow the metal ions and biomolecules getting inside the hydrogels to interact with all active groups on/in the hydrogels in the adsorption applications. Equilibrium swelling ratio of the hydrogels at pH 0.5 is at least half of the equilibrium swelling ratio of the hydrogels at pH 7.0. Oscillatory swelling behavior of poly(NHMMA‐ATU) hydrogels between pH 0.5 and pH 7.0 showed that the hydrogels are quite stable at different pH conditions. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1657–1664, 2006     

pH‐responsive poly(ethylene glycol)‐poly(ϵ‐caprolactone)‐poly(glutamic acid) polymersome as an efficient doxorubicin carrier for cancer therapy

The synthesis, characterization and potential application in the doxorubicin (Dox) delivery system of a biodegradable polypeptide‐based block copolymer, poly(ethylene glycol)₂₀₀₀‐poly(?‐caprolactone)₆₀₀₀‐poly(glutamic acid)₁₀₀₀ (PEG₂₀₀₀‐PCL₆₀₀₀‐PGA₁₀₀₀), was investigated. The copolymer was synthesized via ring‐opening polymerization and characterized by ¹H NMR and Fourier transform IR. The synthesized copolymer could self‐assemble into aggregates and the critical aggregation concentration was 0.23 mg mL^?1. Transmission electron microscopy indicated that spherical polymersomes formed with a desirable size about 180 nm. Therefore Dox was encapsulated into these polymersomes, and then we investigated its applications in a drug delivery system. These Dox‐loaded polymersomes (PolyDox) were characterized by dynamic light scattering, zeta potential and pH responsiveness measurements. In vitro drug release indicated that the release rate of drug from PolyDox was pH‐responsive and significantly decreased. The drug pharmacokinetic parameters were improved in comparison to the group treated with free Dox, which proved the prolonged Dox release from PolyDox. A WST‐1 assay indicated a low toxicity and good compatibility of copolymer to cells within 48 h. The results also showed that PolyDox appeared to induce a higher anti‐tumor effect. Cell uptake results indicated that PolyDox displayed higher cellular uptake in A549 cells. Endocytosis inhibition results demonstrated that the internalization of PolyDox was mostly mediated by the fluid‐phase endocytosis pathway. © 2017 Society of Chemical Industry     

Investigation of thermal behavior of poly(2‐hydroxyethyl methacrylate‐co‐itaconic acid) networks

The thermal behavior of poly(2‐hydroxyethyl methacrylate) [PHEMA] homopolymer and poly(2‐hydroxyethyl methacrylate‐co‐itaconic acid) [P(HEMA/IA)] copolymeric networks synthesized using a radiation‐induced polymerization technique was investigated by differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The glass‐transition temperature (T_g) of the PHEMA homopolymer was found to be 87°C. On the other hand, the T_g of the P(HEMA/IA) networks increased from 88°C to 117°C with an increasing amount of IA in the network system. The thermal degradation reaction mechanism of the P(HEMA/IA) networks was determined to be different from the PHEMA homopolymer, as confirmed by thermogravimetric analysis. It was observed that the initial thermal degradation temperature of these copolymeric networks increased from 271°C to 300°C with IA content. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1602–1607, 2007