pH‐sensitive shrinking of a dextran sulfate/chitosan complex gel and its promotion effect on the release of polymeric substances

A pH‐sensitive gel was prepared by polyelectrolyte complex formation between dextran sulfate and chitosan. When the complex gel contained more amino groups than sulfate groups, it shrank pronouncedly at around pH 7 in NaCl solutions of various concentrations, probably because of the deionization of protonated amino groups remaining free from electrostatic interaction with the sulfate groups. Using the complex gel loaded with dextran by absorption, releasing behaviors were studied under various conditions. It was shown that shrinking of the complex gel had a promotion effect on the release of dextran. In 170 mM NaCl solution, the complex gel released dextran more rapidly at pH 8 than at pH 2, because the degree of shrinking was greater at pH 8. Thus, the promotion effect of the complex gel on the release of dextran was pH dependent, though the release rates at the two pHs became closer as the average molecular weight of dextran loaded was lowered. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 667–674, 2001     

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     

Surfactant‐free thermochromic hydrogel system: PVA/borax gel networks containing pH‐sensitive dyes

The well‐known pH‐indicators, phenolphthalein and bromothymol blue, exhibit an outstanding thermochromism, when they are embedded in aqueous polyvinyl alcohol/borax gel networks. The color of phenolphthalein in hydrogels changes gradually from colorless at 20°C to dark red at 70°C. The pH change in a hydrogel system was from 8.0 to 8.9 with increasing temperature. In the case of bromothymol blue, the color was optically clear green at room temperature and changed to clear blue with increasing temperature. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 890–893, 2004     

Polyanion/gelatin complexes as pH‐sensitive gels for controlled protein release

Polyanion/gelatin complexes including poly(methacrylic acid) (PMAA)/gelatin, poly(acrylic acid) (PAA)/gelatin, and heparin/gelatin are investigated as pH‐sensitive gels for controlled protein release. Polyanions can interact with gelatin and form amorphous precipitates within a certain pH range, which is affected by the polyanion nature. The entrapment efficiency of model proteins (myoglobin, cytochrome c, and pepsin) into the complexes is rather high (>80%). By using a modified colloid titration that mixes a solution of gelatin and model proteins titrated with polyanion solution, myoglobin and cytochrome c are found to interact with polyanions by electrostatic forces at low pH, while pepsin either interacts with the polyanion when the pH is below its isoelectric point (IEP) or complexes with gelatin at a pH above IEP_pepsin. At pH 7.4 all the complexes dissociate and proteins are rapidly released within a few hours. The complexes are stable and the proteins are retained within a certain pH range, which is related to the polyanion type (e.g., 5.0–2.0 for PMAA, 4.6–1.2 for PAA, and <4.3 for heparin). The three processes of complex formation, dissociation, and protein release have a good correlation. In addition, the protein release transition takes place within a rather narrow pH range (ca. 0.5 units) and the protein nature has little effect on the protein release profile. The high protein entrapment efficiency and good pH sensitivity of the protein release can be mainly attributed to the electrostatic attractive interactions between proteins and polyanion or gelatin. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1416–1425, 2001     

pH‐sensitive polymeric particles as smart carriers for rebar inhibitors delivery in alkaline condition

The waste problem of the rebar inhibitors is very serious due to that it is a long time before they can exert their best effect in the concrete and they are kept losing all the time. However, there is still no effective solution to alleviate such situation. Meanwhile, drug delivery control technology based on environmental sensitive polymers has been successfully applied in biomedical fields. Thus, poly(acrylic acid)–acrylamide was synthesized as smart carrier for controlling rebar inhibitors delivery in concrete. Dipotassium hydrogen phosphate as model drug was encapsulated inside the polymeric particles via a self‐assembly process. The pH‐responsive activities of the polymeric particles were estimated by monitoring their swelling performances in solutions of different pH values and the drug delivery control characteristics were studied in simulated concrete pore solutions. The results indicate the polymeric particles deserve network structures with high porosity and exhibit excellent pH‐responsive activities, which can perform as perfect intelligent carriers whereas the releasing of the inhibitors follows the first‐order kinetic law. The work suggests a new application field of drug delivery control technology. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45886.     

Synthesis and characterization of pH‐sensitive networks containing degradable poly(1,3‐dioxolane) segments

pH‐sensitive networks were obtained by radical copolymerization of telechelic poly(1,3‐dioxolane) (PDXLDA) with acrylic acid (AA). PDXLDA was synthesized by acrylation of the corresponding dihydroxylated polyacetal (polyDXL) with AA in pyridine. The copolymer networks of poly(AA‐b‐DXL) showed pH sensitivity due to —COOH groups, which are insoluble in any solvents, but can swell in water or good solvents. The swelling behavior is closely related to the solvents and is composition‐dependent. The networks containing polyDXL segments can be decrosslinked under acidic conditions due to the low ceiling temperature of polyDXL. After degradation, the linear segments of polyDXL became cycled molecules. The networks' structure, swelling behavior, and degradation were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, GC–MS analysis, and swelling data. This kind of material can be potentially used in biosystems, such as in intelligent drug‐delivery systems. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1678–1682, 2002     

Poly(methacrylamide‐co‐acrylic acid) hydrogels for gastrointestinal delivery of theophylline. I. Swelling characterization

pH sensitive copolymeric hydrogels have been synthesized by free‐radical polymerization of methacrylamide and acrylic acid in aqueous medium. The gels were characterized by FTIR spectroscopy, thermogravimetric analysis, and swelling measurements. To determine the suitability of theses hydrogels for gastrointestinal oral delivery of model drug theophylline, their swelling behavior was investigated as a function of pH and various structural parameters such as the average molecular weight between crosslinks, crosslink density, and mesh size were calculated. Likewise initial, average and late time diffusion coefficients were also evaluated in simulating intestinal fluid of pH 6.8 at 37°C. The gel underwent sharp volume phase transition in the vicinity of pH 5.8. The mesh sizes of the hydrogel were between 8.4 and 9.2 Å in the collapsed state (pH range 1–2; SGF) and between 514 and 524 Å in the swollen state (pH range 7–8; SIF). The experimental data was found to fit well to Beren‐Hopfenberg equation thus suggesting that later part of swelling was chain relaxation controlled. The activation energy, as determined from Arrhenius equation was found to be 13.71 kJ mol^?1. Likewise, enthalpy of mixing was also evaluated using Gibbs‐Helmholtz equation. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2995–3008, 2006     

Hollow,pH‐sensitive calcium–alginate/poly(acrylic acid) hydrogel beads as drug carriers for vancomycin release

In this study, hollow calcium–alginate/poly(acrylic acid) (PAA) hydrogel beads were prepared by UV polymerization for use as drug carriers. The hollow structure of the beads was fortified by the incorporation of PAA. The beads exhibited different swelling ratios when immersed in media at different pH values; this demonstrated that the prepared hydrogel beads were pH sensitive. A small amount (<9%) of vancomycin that had been incorporated into the beads was released in simulated gastric fluid, whereas a large amount (≤67%) was released in a sustained manner in simulated intestinal fluid. The observed drug‐release profiles demonstrated that the prepared hydrogel beads are ideal candidate carriers for vancomycin delivery into the gastrointestinal tract. Furthermore, the biological response of cells to these hydrogel beads indicated that they exhibited good biological safety and may have additional applications in tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

A pH‐sensitive porous chitosan membrane prepared via surface grafting copolymerization in supercritical carbon dioxide

We report the successful grafting copolymerization of acrylic acid (AA) on a crosslinked porous chitosan membrane in supercritical carbon dioxide at pressures ranging from 13 to 25 MPa with the use of benzyl peroxide (BPO) as the reduction–oxidation free radical initiator. The effects of reaction pressure, initiator concentration, monomer concentration, reaction temperature and reaction time on grafting yield (GY) were investigated. GY initially increases and then decreases with increasing polymerization temperature and AA and BPO concentrations. The optimum grafting conditions to obtain maximum GY are as follows: 8 h reaction time, 80 °C reaction temperature, 3.05 × 10^?2 g mL^?1 AA concentration, 3 × 10^?3 g mL^?1 BPO concentration and 16 MPa reaction pressure. The water flux of the grafted chitosan membranes decreases with pH from 2 to 7, even at considerably low GY (0.95 wt%). A novel and green modification method has been developed for the preparation of biopolymer‐based membranes. © 2014 Society of Chemical Industry     

Synthesis,characteristics, and phase behavior of a thermosensitive and pH‐sensitive polyelectrolyte

A series of poly(N‐isopropylacrylamide‐co‐methacrylic acid‐co‐octadecyl acrylate) (poly(NIPAM‐co‐MAA‐co‐ODA)) with different monomer molar ratios was synthesized. Critical micelle concentration (CMC) of the polyelectrolyte solution was determined and the CMC increase with methacrylic acid content in the polyelectrolyte. The phase behaviors of the polyelectrolyte solution were studied, and the effects of various factors on the phase transition were discussed. The experimental results indicate that the lower critical solution temperature and the phase transition pH depend on the monomer molar ratio in the polyelectrolyte. Effect of polyelectrolyte concentration on phase transition pH was studied, and results shown that the phase‐transition pH is independent of the polyelectrolyte concentration. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and pH‐sensitivity of polyacrylonitrile (PAN) based porous hollow gel fibers

Polyacrylonitrile based porous hollow gel fibers were prepared from PAN hollow fibers by oxidation and subsequent alkaline treatment. Fourier‐transform infrared (FTIR), X‐ray diffraction, and scanning electron microscope (SEM) analyses showed that the PAN porous hollow gel fiber was a kind of amphoteric fiber due to the combination of cationic groups of pyridyl and anionic groups of carboxyl; after gelation the hollow channel and finger‐like pores on the fiber walls were conserved. The effects of cyclization reaction degree, alkaline solution concentration, and alkaline treatment time on the mechanical properties or pH‐sensitive behavior of the porous hollow gel fibers were investigated. The elongation/contraction behavior was studied in detail. It was found that the gel fiber exhibited a large swelling in an alkaline solution and contracting in an acid solution; the swelling change in length was above 90%; the responsive time of elongation/contraction was less than 20 s; the maximum contraction force was 20 N/cm²; and pH‐sensitivity was reversible. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A novel pH‐sensitive gelatin–DNA semi‐interpenetrating polymer network hydrogel

Gelatin and DNA were mixed together in various ratios followed by the addition of glutaraldehyde as a cross‐linker. FT‐IR spectroscopy confirmed the formation of a semi‐interpenetrating polymer network (semi‐IPN) between the gelatin and DNA. The gelatin–DNA semi‐IPN hydrogel underwent, reversibly, remarkable changes in swelling degree in response to the variation of pH. In the low‐pH range, the hydrogel showed a lower swelling degree; with an increment in pH, the hydrogel was highly swollen, which is considered to originate from the complexation and de‐complexation between gelatin and DNA, as was verified by turbidity measurements. Higher contents of DNA result in an increase in the swelling degree, which is presumably due to the easy outward expansion of free DNA moieties. The permeability coefficient, P, for a model molecule, cimetidine, through the semi‐IPN hydrogel membranes was determined in pH 1.0 and pH 12.0 buffer solutions. The results show that the permeation of cimetidine is responsive to pH change, and an evident variation in the P values occurs in response to the pH of the media. Copyright © 2004 Society of Chemical Industry     

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     

A novel amphoteric,pH‐sensitive,biodegradable poly[chitosan‐g‐(L‐lactic‐co‐citric) acid] hydrogel

The novel amphoteric, pH‐sensitive, biodegradable poly([chitosan‐g‐(L ‐lactic‐co‐citric) acid]) hydrogel (CLC) was synthesized through the reaction of chitosan (CS) with poly(L ‐lactic‐co‐citric acid) (PLCA). The structure of CLC was characterized by Fourier transform infrared spectroscopy, elemental analysis, and wide‐angle X‐ray diffraction measurement. The degree of substitution of CS amino groups was evaluated from salicylaldehyde analysis. The swelling behavior of CLC film in an aqueous solution with various pHs and the apparent swelling kinetics were studied. The swelling mechanisms of CLC film in acidic and alkaline mediums are discussed. The results showed that CLC hydrogel had a higher degree of swelling in the pH range of 4 > pH > 8 and that the swelling rate order in different buffers was neutral > acidic > basic mediums. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3850–3854, 2003     

Stimuli sensitive copolymer poly(N‐tert‐butylacrylamide‐ran‐acrylamide): Synthesis and characterization

Temperature sensitive random linear and crosslinked copolymers of N‐tert‐butylacrylamide (NTBA) and acrylamide (Am) were synthesized by the solution polymerization method, using regulated dosing of comonomer Am having a higher reactivity ratio (r_Am = 1.5) than NTBA (r_NTBA = 0.5). Copolymers with varying feed ratios of NTBA and Am (80 : 20 to 20 : 80 mol %) were synthesized and characterized. For the synthesis of copolymer hydrogels, N′, N‐methylene bisacrylamide (MBA) (1.13 mol %) was used along with monomers. The effect of composition on transition properties was evaluated for the linear copolymers and their hydrogels. A definite trend was observed. The incorporation of a higher percentage of the hydrophilic comonomer Am in the structure resulted in the shifting of the transition temperature towards a higher value. The transition temperatures of the copolymers synthesized with feed compositions of 80 : 20, 70 : 30, 60 : 40, 50 : 50, 40 : 60, 30 : 70, and 20 : 80 mol % were found to be 2, 10, 19, 27, 37, 45, and 58°C, respectively. Differential scanning calorimetry (DSC) studies confirmed the formation of random copolymers. The copolymers synthesized with a monomer feed ratio of 50 : 50 with regulated dosing showed a single glass transition temperature (T_g) at 168°C, while the copolymer synthesized with full dosing of Am at the beginning of the reaction showed two T_gs, at 134 and 189°C. The copolymer samples were analyzed by Fourier transform infrared spectroscopy (FTIR) for ascertaining the composition. The composition of the copolymers followed the trend of the feed ratio, but the incorporation of NTBA in the copolymers was found to be lower than the feed ratio because of lower than quantitative yields of the reactions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 672–680, 2005     

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     

Influence of the copolymer architecture and composition on the response and mechanical properties of pH‐sensitive fibers

A series of copolymers based on acrylonitrile (AN) and acrylic acid (AA) with varying architecture and composition were synthesized using free radical polymerization. The distribution of monomers in the copolymer chains could be successfully controlled by regulating the addition of more reactive monomer (AA). Copolymers having nearly random distribution of comonomer moieties to block type distribution with different composition (10–50 mol % AA) were synthesized to investigate the effect of polymer architecture and composition on pH response and mechanical properties of resultant structures. These copolymers were solution spun from dimethylformamide‐water system, drawn in coagulation bath, and annealed at 120°C for 2 h to make pH‐sensitive fibers which were structurally stable without the need of chemical crosslinking. The fibers from block copolymers showed significantly better tensile strength (34.3 MPa), higher retractive forces (0.26 MPa), and enhanced pH response (swelling 3890%) in comparison with fibers from random copolymer (13.55 MPa, 0.058 MPa, and 1723%, respectively). The tensile strength and retractive forces could be further improved to a value of 72 MPa and 0.36 MPa, respectively, by changing the composition of the block copolymer while retaining the swelling percentage similar to the random copolymer mentioned above. It is proposed that on processing to fibers, the block copolymers could form a segregated domain structure with separate domains of AA and AN, where AN domains were responsible for high structural integrity by providing connectivity among polymer chains, while AA domains showed improved response to changing pH of the environment. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Thermo‐ and pH‐sensitive hydrogels based on 2‐(2‐methoxyethoxy)ethyl methacrylate and methacrylic acid

Hydrogels based on commercially available 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA), with methacrylic acid (MAA) as comonomer, are studied. The incorporation of an ionizable monomer, such as MAA, in a thermosensitive system leads to the formation of hydrogels able to respond to pH and temperature according to their monomeric composition. Thus, at low pH, the acid groups of MAA are protonated, and they do not contribute to increase the hydrophilic balance, and collapse of the hydrogels occurs around room temperature. For temperatures below that of collapse, the degree of swelling increases with increasing MEO₂MA content. In contrast, at neutral or basic pH, the ionization of the acid groups contributes to increase the hydrophilicity and the osmotic pressure, leading to polyelectrolyte behaviour. In this regime, the swelling capacity increases and the thermosensitivity decreases with increasing MAA content in the hydrogels. These properties make poly(MEO₂MA‐co‐MAA) hydrogels suitable candidates for use in oral controlled delivery of hydrophobic drugs. This possibility is explored using ibuprofen as a model drug, after a complete study of the swelling kinetics. Copyright © 2010 Society of Chemical Industry     

Swelling behavior of pH‐ and temperature‐sensitive copolymers containing 2‐hydroxy‐ethyl methacrylate and N‐vinyl‐2‐pyrrolidone crosslinked with new crosslinkers

Copolymers of 2‐hydroxyethyl methacrylate (HEMA) and N‐vinyl‐2‐pyrrolidone (VP) and homopolymers of HEMA and VP were crosslinked in the presence of different mol% of melamine trimethacrylamide (MMAm) and melamine triacrylamide (MAAm) as crosslinkers by bulk radical polymerization. The resultant xerogels were characterized by extracting the soluble fractions and measuring the equilibrium water content. Lower critical solution transition temperatures (LCST) were measured by DSC. The properties of crosslinked HEMA and VP copolymers, VP and HEMA series were evaluated in terms of compositional drift of polymerization, heterogeneous crosslinking, and chemical structure of the relevant components. Soluble fractions of the crosslinked networks were reduced by varying the MAAm and MMAm concentrations. The influence of environmental conditions such as temperature and pH on the swelling behavior of these polymeric gels was investigated. The swelling behaviors of the resulting gels show pH sensitivity. This behavior is explained on the basis that amide groups of VP or crosslinkers could be hydrolyzed to form negatively charged carboxylate ion groups in the produced networks in response to an external pH variation. Copyright © 2004 Society of Chemical Industry     

pH‐sensitive swelling and release behaviors of anionic hydrogels for intelligent drug delivery system

The pH‐sensitive swelling and release behaviors of the anionic P(MAA‐co‐EGMA) hydrogels were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. There was a drastic change of the equilibrium weight swelling ratio of P(MAA‐co‐EGMA) hydrogels at a pH of around 5, which is the pK_a of poly (methacrylic acid) (PMAA). At a pH below 5, the hydrogels were in a relatively collapsed state but at a pH higher than 5, the hydrogels swelled to a high degree. When the molecular weight of the pendent poly(ethylene glycol) (PEG) of the P(MAA‐co‐EGMA) increased, the swelling ratio decreased at a pH higher than 5. The pK_a values of the P(MAA‐co‐EGMA) hydrogels moved to a higher pH range as the pendent PEG molecular weight increased. When the feed concentration of the crosslinker of the hydrogel increased the swelling ratio of the P(MAA‐co‐EGMA) hydrogels decreased at a pH higher than 5. In release experiments using Rhodamine B (Rh‐B) as a model solute, the P(MAA‐co‐EGMA) hydrogels showed a pH‐sensitive release behavior. At low pH (pH 4.0) a small amount of Rh‐B was released while at high pH (pH 6.0) a relatively large amount of Rh‐B was released from the hydrogels. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007