Selected properties of pH‐sensitive,biodegradable chitosan–poly(vinyl alcohol) hydrogel

Chitosan and poly(vinyl alcohol) (PVA) were used to form a semi‐interpenetrating polymeric network with glutaraldehyde as the cross‐linker. The molecular weight and degree of deacetylation of the chitosan were 612 kDa and 72 %, respectively. The chemical bonds formed by the cross‐linking reaction and transition of these bonds in different pH media were investigated. The gelation property of the chitosan–PVA pregel solution and mechanical properties of the hydrogel were studied. The FTIR spectra of the hydrogel before and after swelling at pH 3 and pH 7 indicated formation of Schiff's base (C?N) and ? NH₃⁺. They also showed pH‐induced transition of C?N to C? N, and ? NH₃⁺ to ? NH₂, as well as the instability of the Schiff's base. The chitosan is essential for hydrogel formation through Schiff's base reaction between the amino groups of the chitosan and the aldehyde groups of the glutaraldehyde. The addition of PVA improved the mechanical properties of the hydrogel. However, PVA tends to leach out at longer swelling times in the acidic medium due to hydrolysis of the gel networks, Schiff's base. Copyright © 2004 Society of Chemical Industry     

Structural change and swelling mechanism of pH‐sensitive hydrogels based on chitosan and D,L‐lactic acid

Graft copolymerization of D,L ‐lactic acid (LA) onto chitosan (CS) was attempted without using a catalyst. pH‐sensitive hydrogels were obtained which are based on two different components: a natural polymer and a synthetic polymer. These polyester substituents provide the basis for hydrophobic interactions that contribute to the formation of hydrogels. The swelling mechanisms in enzyme‐free simulated gastric fluid (SGF, pH 2.2) or simulated intestinal fluid (SIF, pH 7.4) at 37°C were investigated. Meanwhile, structural changes of the graft copolymers in the different pH buffers were studied by FTIR, and these are discussed together with the swelling mechanisms. The effect of pH on the water uptake of hydrogel was investigated by using McIlvaine buffer with the same ionic strength. The morphological change of hydrogels in different aqueous solutions is investigated by scanning electron microscopy (SEM). © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3186–3192, 1999     

Synthesis and characterization of novel pH‐sensitive chitosan‐poly(acrylamide‐co‐itaconic acid) hydrogels

Novel pH‐sensitive chitosan‐poly(acrylamide‐co‐itaconic acid) hydrogels were prepared by free radical copolymerization of acrylamide and itaconic acid (IA) in chitosan solution. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry and the swelling ratios of the hydrogels in water (pH 6.8) and pH 1.2. The influence of composition on the thermal properties of the hydrogels was assessed. The glass transition temperatures of the samples increased with IA content, ranging from 110 to 136 °C. Swelling of the hydrogels was found to obey second‐order kinetics with respect to the remnant swelling, indicating that diffusion is controlled by the relaxation of chains. The equilibrium swelling degree was strongly dependent on pH and composition. At both pH values the highest water uptake was obtained for the IA‐free sample M1. From the equilibrium swelling results the average molar mass between crosslinks, M_c, and the crosslink density of the chitosan‐poly(acrylamide‐co‐itaconic acid) samples were calculated. The results evidenced the reinforcing effect of IA on the hydrogel structure. It is concluded that these highly swellable pH‐sensitive hydrogels can be useful for applications in biomedicine and pharmacy. © 2013 Society of Chemical Industry     

Water‐assisted formation of honeycomb films of poly(L‐lactic‐co‐glycolic acid)

The ordered honeycomb structures of poly(L ‐lactic‐co‐glycolic acid) and poly(D ,L ‐lactic‐co‐glycolic acid) fabricated in a humid atmosphere were reported in this paper. It was found that surfactants were important in the formation of honeycomb films of hydrophobic polymer. The affecting factors, such as the environment temperature, the atmosphere humidity, and the concentration of the polymer solution of the honeycomb porous structure, were also tested. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1013–1018, 2006     

Synthesis and characterization of fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels

BACKGROUND: A considerable amount of research has been focused on smart hydrogels that can respond to external environmental stimuli, especially temperature and pH. In this study, fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels were prepared by free radical copolymerization in aqueous solution using poly(ethylene glycol) (PEG) as a pore‐forming agent. RESULTS: Swelling studies showed that the hydrogels produced had both temperature and pH sensitivity. The deswelling kinetics at high temperature demonstrated that the shrinking rates were influenced by the addition of the pore‐forming agent and the amount of acrylic acid in the initial total monomers. The deswelling curves in low‐buffer solutions had two stages. Pulsatile swelling studies indicated that the PEG‐modified hydrogels were superior to the normal ones. These different swelling properties were further confirmed by the results of scanning electron microscopy. CONCLUSION: Such fast responsive thermo‐ and pH‐sensitive hydrogels are expected to be useful in biomedical fields for stimuli‐responsive drug delivery systems. Copyright © 2008 Society of Chemical Industry     

Comparison of poly(aspartic acid) hydrogel and poly(aspartic acid)/gelatin complex for entrapment and pH‐sensitive release of protein drugs

Biodegradable poly(aspartic acid) (PASP) hydrogel and PASP/gelatin complex were prepared to evaluate their potential application as pH‐sensitive matrices for controlled protein release. Entrapment of myoglobin (Mb) and its release were compared between the two types of carriers. It was found that incorporation of Mb into PASP hydrogel strongly depended on the medium pH and NaCl concentration, and was time‐consuming. However, complete entrapment of Mb into PASP/gelatin complex was found within pH ranged from 2.5 to 4.0, which was concomitant with the formation of PASP/gelatin complex. By adjusting Mb feed ratio, Mb entrapment in the complex can be up to 31.54% (by weight) with high loading efficiency (96.2%). Gradual release of Mb from PASP hydrogel was observed within pH 2.0–7.4, while Mb release from PASP/gelatin complex was negligible within pH 2.0–4.2 for 4 days. In addition, pulsatile Mb release can be achieved by combining polyanhydride with pH‐sensitive PASP/gelatin complex, while the device composed of polyanhydride and PASP hydrogel is mechanically unstable. PASP/gelatin complex formed by electrostatic interactions is superior to the single‐component PASP hydrogel synthesized by chemical cross‐linking as pH‐sensitive matrices for controlled protein release when entrapment of proteins and pH‐sensitivity of protein release are concerned. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Formation of ordered microporous films with water as templates from poly(D,L‐lactic‐co‐glycolic acid) solution

Recently a method that uses water droplets at the air–solution interface as an ordered template was reported for the preparation of ordered micrometer‐size honeycomb structures. Here we show that the method can also be used for formation of honeycomb‐like porous films from random copolymers with certain hydrophilicity, besides those polymers with defined structures such as block copolymers, starlike homopolymers, amd amphiphilic polymers. This demonstrates that the stabilization of water droplets is the key factor for the regular structure. Also we indicate that size and structure of the films can be regulated by such variables as concentration and atmospheric humidity. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1846–1850, 2003     

Swelling properties of CMC‐g‐poly (AAm‐co‐AMPS) superabsorbent hydrogel

A series of biopolymer‐based superabsorbent hydrogels based on carboxymethyl cellulose has been prepared by free‐radical graft copolymerization of acrylamide and 2‐acrylamido‐2‐methylpropan sulfonic acid (AMPS) in aqueous solution using methylenebisacrylamide as a crosslinking agent and ammonium persulfate as an initiator. The effect of variables on the swelling capacity such as: acrylamide/AMPS weight ratio, reaction temperature, and concentration of the initiator and crosslinker were systematically optimized. The results indicated that with increasing the amount of AMPS, the swelling capacity is increased. FT‐IR spectroscopy and scanning electron microscope analysis were used to confirm the hydrogel structure. Swelling measurements of the synthesized hydrogels in different salt solutions indicated considerable swelling capacity. The absorbency under load of the superabsorbent hydrogels was determined by using an absorbency under load tester at various applied pressures. A preliminary swelling and deswelling behaviors of the hydrogels were also studied. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Hydroxyethyl chitosan‐g‐poly(acrylic acid‐co‐sodium acrylate) superabsorbent polymers

A novel hydroxyethyl chitosan‐g‐poly(acrylic acid‐co‐Sodium Acrylate) (HECTS‐g‐(PAA‐co‐PSA)) superabsorbent polymer was prepared through graft copolymerization of acrylic acid and sodium acrylate onto the chain of hydroxyethyl chitosan. The structure of the polymer was characterized by FTIR. By studying the water absorption of the polymer synthesized under different conditions, the optimal conditions for synthesizing the polymer with the highest swelling ratio was defined. This superabsorbent polymer was further treated by the solvent precipitation method and by the freeze‐drying method. We found that the water absorption rate of the treated polymer was greatly increased and the microstructure of the treated polymer was changed from small pores to loose macro pores. The swelling processes of the polymers before and after modification fit first‐order dynamic processes. The amount of the residual acrylic acid was greatly decreased after treatments. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis of poly(N,N‐diethylacrylamide‐co‐acrylic acid) hydrogels with fast response rate in NaCl medium

A series of thermo‐ and pH‐sensitive poly (N,N‐diethylacrylamide‐co‐acrylic acid) (P(DEA‐co‐AA)) hydrogels were prepared in NaCl aqueous solutions with different concentrations. Swelling and deswelling studies showed that in comparison with conventional P(DEA‐co‐AA) hydrogels (prepared in distilled water), the P(DEA‐co‐AA) hydrogels thus prepared had almost the same volume phase transition temperature (VPTT), but exhibited much faster response rates as the temperature was raised above their VPTT. Besides, the hydrogels prepared by this method had faster response rates in low pH buffer solutions, and the response rates increased with the increased concentration of the NaCl solutions used during the polymerization. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Reactive blending of poly(L‐lactic acid) with poly(ethylene‐co‐vinyl alcohol)

Poly(L ‐lactic acid) (PLLA) was blended with poly(ethylene‐co‐vinyl alcohol) (EVOH) in the presence of an esterification catalyst to induce reaction between the hydroxyl groups of EVOH and the terminal carboxylic group of PLLA. Nascent low‐molecular‐weight PLLA, obtained from a direct condensation polymerization of L ‐lactic acid in bulk state, was used for the blending. Domain size of the PLLA phase in the graft copolymer was much smaller than that corresponding to a PLLA/EVOH simple blend. The mechanical properties of the graft copolymer were far superior to those of the simple blend, and the graft copolymer exhibited excellent mechanical properties even though the biodegradable fraction substantially exceeded the percolation level. The grafted PLLA reduced the crystallization rate of the EVOH moiety. Melting peak temperature (T_m) of the PLLA phase was not observed until the content of PLLA in the graft reaction medium went over 60 wt %. The modified Sturm test results demonstrated that biodegradation of EVOH‐g‐PLLA took place more slowly than that of an EVOH/PLLA simple blend, indicating that the chemically bound PLLA moiety was less susceptible to microbial attack than PLLA in the simple blend. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 886–890, 2005     

Synthesis and swelling properties of pH‐sensitive hydrogels based on chitosan and poly(methacrylic acid) semi‐interpenetrating polymer network

A novel semi‐interpenetrating polymer network (semi‐IPN) hydrogel composed of chitosan and poly(methacrylic acid) was synthesized using formaldehyde as a crosslinker. The amount of crosslinker was searched and optimized. The structure of the hydogel was investigated by Fourier transform infrared (FTIR) spectroscopy. The spectrum shows that a structure of polyelectrolyte complex exists in the hydrogel. The effects of pH, ionic strength, and inorganic salt on the swelling behaviors of the hydrogel were studied. The results indicate the hydrogel has excellent pH sensitivity in the range of pH 1.40 to 4.50, pH reversible response between pH 1.80 and 6.80, and ionic strength reversible response between ionic strength 0.2 and 2.0M. The results also show that the hydrogel has a bit higher swelling capacity in a mix solution of calcium chloride (CaCl₂) and hydrochloric acid (HCl) solution than in a mix solution of sodium chloride (NaCl) and HCl. These results were further confirmed through morphological change measured by scanning electron microscope (SEM). © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1720–1726, 2005     

Effect of attapulgite contents on release behaviors of a pH sensitive carboxymethyl cellulose‐g‐poly(acrylic acid)/attapulgite/sodium alginate composite hydrogel bead containing diclofenac

A series of pH‐sensitive composite hydrogel beads, carboxymethyl cellulose‐g‐poly(acrylic acid)/attapulgite/sodium alginate (CMC‐g‐PAA/APT/SA), were prepared by combining CMC‐g‐PAA/APT composite and SA, using Ca²⁺ as the ionic crosslinking agent and diclofenac sodium (DS) as the model drug. The effects of APT content and external pH on the swelling properties and release behaviors of DS from the composite hydrogel beads were investigated. The results showed that the composite hydrogel beads exhibited good pH‐sensitivity. Introducing 20% APT into CMC‐g‐PAA hydrogel could change the surface structure of the composite hydrogel beads, decrease the swelling ability, and relieve the burst release effect of DS. The drug cumulative release ratio of DS from the hydrogel beads in simulated gastric fluid was only 3.71% within 3 hour, but in simulated intestinal fluid about 50% for 3 hour, 85% for 12 hour, up to 90% after 24 hour. The obtained results indicated that the CMC‐g‐PAA/APT/SA hydrogel beads could be applied to the drug delivery system as drug carriers in the intestinal tract. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Deformation kinetics of pH‐sensitive hydrogels

Polymeric gels can undergo large deformation when subjected to external solutions of varying pH. It is imperative to understand the deformation process of pH‐sensitive hydrogels for the effective application of these attractive materials in the biomedical and microfluidic fields. In the modeling of these multi‐phase materials, finite element (FE) modeling is a useful tool for the development of future applications, and it allows developers to test a wide variety of material responses in a cost‐effective and efficient manner, reducing the need to conduct extensive laboratory experiments. Although a FE user‐defined material model is available for the equilibrium state, the transient response of pH‐sensitive gels has not been effectively modeled. Based on our recent work using the heat transfer analogy to tap into the readily available coupled temperature–displacement elements available in the commercial FE software ABAQUS for simulation of the transient swelling process of neutral hydrogels, the transient swelling process of a pH‐sensitive hydrogel is studied and a FE model is further developed to simulate the transient phenomena. Some benchmark examples are investigated to demonstrate the model's capabilities in the simulation of nonlinear deformation kinetics relevant to several applications of pH‐sensitive hydrogels. © 2013 Society of Chemical Industry     

Swelling of pH‐sensitive chitosan–poly(vinyl alcohol) hydrogels

The swelling properties of different chitosan–poly(vinyl alcohol) (PVA) hydrogels were investigated as functions of the medium pH and salt concentration. The maximum swelling ability of the hydrogels was at a buffer pH of approximately 3, regardless of the PVA content in the hydrogels. The maximum mass of the swollen hydrogels was about 13 times that of their contracted counterparts. The cyclical swelling and contraction between pH 3 and pH 7 buffers and pH 3 and pH 3 buffers with salt confirmed the Donnan swelling mechanism of these hydrogels. The swelling mechanism was considered the transfer of water molecules driven by a concentration gradient. This was represented by a simplified mass‐balance model, which neglected the effect of the ionization reaction, for the initial swelling period. The effective mass‐transfer coefficient of water molecules during swelling, estimated with this model, gradually decreased with increasing PVA content in the hydrogels. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4665–4671, 2006     

Poly(D,L‐lactide‐co‐glycolide)/poly(ethylenimine) blend matrix system for pH sensitive drug delivery

Poly(D ,L ‐lactide‐co‐glycolide) (PLGA) and poly(ethylenimine) (PEI) were blended and found to form a homogeneous pH sensitive matrix for drug release. Differential scanning calorimetry (DSC) studies of the PLGA/PEI blends showed a single glass transition temperature at all compositions. Fourier transform infrared spectroscopy (FTIR) demonstrated that the PLGA carbonyl peak at 1760 cm^?1 shifted to 1666 cm^?1 as a result of amide bond formation between the two polymers. This was confirmed by ¹³C nuclear magnetic resonance studies. A PLGA/PEI matrix of 90/10 weight ratio was chosen for evaluation for controlled drug release. Both hydrophobic β‐lapachone and hydrophilic rhodamine B showed pH dependent release profiles with faster release kinetics at lower pH values. The observed pH sensitive drug release was mainly attributed to two factors, pH dependent swelling and protonation of the PEI‐PLGA matrix. These results demonstrate utility of a PLGA/PEI matrix and its potential application in pH responsive drug delivery. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 89–96, 2006     

β‐cyclodextrin/poly(vinyl alcohol) hydrogels containing phenylpropionic acid and naphthylamine: dual pH‐sensitive release

Hydrogel composed of β‐cyclodextrin (β‐CD) and poly(vinyl alcohol) was prepared in a strong alkaline condition using epichlorohydrin as a crosslinker. Phenylpropionic acid (PPA) and naphthylamine (NA) were loaded in the cavities of β‐CD residues to endow the hydrogel with a dual pH‐sensitive characteristic. In release experiments using fluorescein isothiocyanate‐dextran (FITC‐dextran) as a dye, PPA/NA‐loaded hydrogel exhibited an extensive release not only in acidic conditions (e.g. pH 3.0) but also in alkaline conditions (e.g. pH 9.0). PPA and NA will be highly ionized at the alkaline and the acidic pH and they could promote swelling of the hydrogel, causing an extensive release at those pH values. However, the release was suppressed at mid pH values (e.g. pH 5.0 and pH 7.4), possibly due to the formation of salt bridges between PPA^? and NA⁺. In fact, the degree of swelling at mid pH was lower than that observed at strong acidic pH and alkaline pH. According to SEM images, the pore size and the texture compactness of hydrogels which had been subjected to swelling at different pH values could also account for the dual pH‐sensitive releases. The hydrogels exhibited dual pH sensitivities in terms of FITC‐dextran release and swelling. These hydrogels might be used as a pH‐sensitive vehicle for water‐soluble drugs. © 2013 Society of Chemical Industry     

Control of release characteristics in pH‐sensitive poly(vinyl alcohol)/poly(acrylic acid) microcapsules containing chemically treated alumina core

The pH‐sensitive poly(vinyl alcohol)/poly(acrylic acid) hydrogel microcapsules containing vitamin B₁₂‐loaded Al₂O₃ core were prepared with a three‐step emulsion polymerization. Al₂O₃ was chemically treated with HCl or NaOH solutions at room temperature for 24 h to modify the binding properties with vitamin B₁₂. The colon‐targeted release characteristics of vitamin B₁₂ from the microcapsules were evaluated at different pHs. These microcapsules showed the faster and larger release of vitamin B₁₂ due to the high swelling of microcapsule shell as the pH was changed into more basic condition. However, these microcapsules showed the slower and less release of vitamin B₁₂ as the acid value of Al₂O₃ increased due to the strong binding interaction between Al₂O₃ core and vitamin B₁₂ even though the initial loading of vitamin B₁₂ was higher. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

A convenient one‐step preparation of chitosan‐poly(sodium acrylate‐co‐acrylamide) hydrogel hybrids with super‐swelling properties

Hydrogel hybrids were conveniently prepared from alkaline hydrolysis of chitosan–poly(acrylonitrile) mixture under highly practical conditions. The reaction of chitosan alkoxide anions with nitrile groups of poly(acrylonitrile) (PAN) forms crosslinking points and results in a three‐dimensional network with superswelling ability in aqueous media. The hydrogel hybrid was identified using FTIR spectroscopy. The PAN content of the hydrolyzing feed affects proportionally the swelling capacity of the hydrogel hybrid. The swelling properties (capacity and rate) of the ampholytic hydrogel were investigated preliminarily. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1615–1619, 2006     

Investigation of pH sensitivity of poly(acrylic acid‐co‐acrylamide) hydrogel

It was found that the upper critical solution temperature (UCST) of poly(acrylic acid‐co‐acrylamide) hydrogel decreases with increase in pH. The UCST of samples equilibrated in a buffer at pH 2.5 was 33.7 °C, whereas it shifted to below 0 °C when swollen in buffers above pH 10. FT‐IR showed that COOH group of acrylic acid ionized gradually in alkaline media. The morphology change of the hydrogel swollen in different buffers was studied by environmental scanning electron microscopy (ESEM). ESEM images showed that the pore size of the sample increased with increase in pH, and in strongly basic media the three‐dimensional network was replaced by a ‘sausage‐like’ or ‘desert‐like’ structure. A study of the pH‐dependent release of cefazolin sodium was also carried out. Copyright © 2003 Society of Chemical Industry