Diffusion and controlled release characteristics of pH-sensitive poly(2-(dimethyl amino)ethyl methacrylate-co-2-hydroxyethylacrylate) hydrogels

The authors describe a facial development of pH-responsive hydrogels composed of 2-(dimethylamino)ethylmethacrylate and 2-hydroxyethylacrylate via free-radical polymerization at 29°C. The hydrogels were characterized by FTIR, SEM, and XRD studies. The diffusional exponent (n), hydrogel network parameters such as average molecular weight between crosslinks (M_c), and polymer-solvent interaction (χ) were calculated by using swelling data. The hydrogels were encapsulated with 5-fluorouracil, the in vitro release data indicated that the maximum drug release was significantly achieved in pH 1.2 rather than in pH 7.4 and it was enhanced up to 30 h. These results suggested that the gels are highly useful for anticancer drug delivery applications.     

Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly(vinyl alcohol) hydrogels

In the present work, a series of cross-linked LVCS/PVA hydrogels with various feed compositions were prepared using glutaraldehyde as cross-linking agent. The prepared hydrogels were used for dynamic and equilibrium swelling studies. The swelling behavior of these hydrogels was investigated as functions of effect of pH, polymeric compositions and degree of cross-linking. Swelling studies were performed in 0.05 M USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing PVA contents in the structure of hydrogels in solutions of higher pH values. This is due to the presence of more hydroxyl groups (–OH) in the PVA structure. On the other hand, by increasing LVCS contents, swelling increased in a solution of acidic pH and it is due to ionization of amino groups (–NH₂), but this swelling was not significant. Swelling of hydrogels was decreased with increase in cross-linking ratio due to tighter hydrogel structure. Porosity and sol–gel fraction were also investigated. It was found that with increase in LVCS and PVA contents porosity and gel fraction increased, whereas by increasing glutaraldehyde content gel fraction increased and porosity decreased. Diffusion coefficient (D) and network parameters, i.e., the average molecular weight between cross-links (M _C), solvent interaction parameters (χ), polymer volume fraction in swollen state (V _2S) and cross-linked density (q) were calculated using Flory–Rehner theory. Selected samples were loaded with model drug diphenhydramine HCl. The release of diphenhydramine HCl was studied for 12 h period in 0.05 M USP phosphate buffer solutions of varying pH 1.2, 5.5 and 7.5. It was observed that drug release increased with increasing PVA contents in the hydrogels, while release of drug decreased as the ratio of cross-linking agent increased in the hydrogel structure owing to strong physical entanglements between polymers. The release mechanisms were studied by fitting experimental data to model equations like zero order, first order, Higuchi and Peppas. Results showed that the kinetics of drug release from hydrogels in buffer solutions of pH 1.2, 5.5 and 7.5 was mainly non-fickian diffusion. Hydrogels were characterized by Fourier transform infrared and X-ray diffraction to confirm the structure and study the crystallinity of hydrogel, respectively.     

Sustained release of potassium diclofenac from a pH‐responsive hydrogel based on gum arabic conjugates into simulated intestinal fluid

This work describes the preparation, the swelling properties and the potassium diclofenac (KDF) release profile of hydrogels of gum arabic (GA), N′,N′‐dimethylacrylamide, and methacrylic acid. In order to convert GA into a hydrogel, the polysaccharide was vinyl‐modified with glycidyl methacrylate. The hydrogels showed pH‐responsive swelling changes, which were more expressive in the basic environment. Release data of KDF were adjusted to a diffusion‐based kinetic model that provides an important insight on affinity of the drug for hydrogel and solvent, which may be the leading parameter for release of guest molecules from polymers. The KDF release from the hydrogels into simulated intestinal fluid decreases when the amount of modified GA increases. This was demonstrated to be due to the higher affinity of KDF for GA‐richer hydrogel, which makes the anti‐inflammatory release less favorable. The analysis of released drug half‐time (t_1/2 = 16.10 and 21.51 h) indicated sustained release characteristics. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43319.     

Synthesis and Characterization of pH Sensitive Poly (Hydroxy Ethyl Methacrylate-co-acrylamidoglycolic Acid) Based Hydrogels for Controlled Release Studies of 5-Fluorouracil

Hydrogels were prepared from 2-hydroxy ethyl methacrylate and acrylamidoglycolic acid using N,N’-methylene bis acrylamide as a crosslinking agent in presence of potassium persulfate initiator. The average molecular mass between crosslinks (M _c) and polymer-solvent interaction parameter of hydrogels were determined from equilibrium swelling values. Fourier transform infrared spectroscopy of hydrogels shows the confirmation of the formation of co-polymeric hydrogels. Scanning electron microscopy of hydrogels shows the porous network structure. Differential scanning calorimetry and X-ray diffraction were performed to understand the crystalline nature of hydrogel and drug after encapsulation in to hydrogels. In vitro release studies indicated the release of 5-Fluorouracil for more than 12 h.     

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     

Crosslinked poly(vinyl alcohol) hydrogels as swollen elastic networks

Transparent crosslinked PVA hydrogels were prepared by electron beam irradiation of aqueous solutions under nitrogen. These weak hydrogels, upon swelling at 30°C in water, showed low elastic moduli (up to 50 psi), low ultimate tensile strength (up to 4 psi), and low extensibility to break (not higher than 85%). Values of the molecular weight between crosslinks M_c were calculated from swelling and from tensile experiments. In fact, two values of M_c were calculated for each swelling experiment, (a) allowing for observed variation in the polymer–solvent interaction parameter χ₁ with concentration, and (b) fixing χ₁ = 0.494 according to literature data. The correlation of the M_c obtained from tensile data with the M_c obtained from swelling data, by (a) or (b), was approximately linear and gave the same per cent agreement.     

Synthesis of biodegradable thermo- and pH-responsive hydrogels for controlled drug release

Novel intelligent hydrogels composed of biodegradable and pH-sensitive poly(l-glutamic acid) (PGA) and temperature sensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (PNH) were synthesized and characterized for controlled release of hydrophilic drug. The influence of pH on the equilibrium swelling ratios of the hydrogels was investigated. A higher PNH content resulted in lower equilibrium swelling ratios. Although temperature had little influence on the swelling behaviors of the hydrogels, the changes of optical transmittance of hydrogels as a function of temperature were marked, which showed that the PNH part of hydrogel exhibited hydrophobic property at temperature above the lower critical solution temperature (LCST). The biodegradation rate of the stimuli-sensitive hydrogels in the presence of enzyme was directly proportional to the PGA content. Lysozyme was chosen as a model drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and the release data suggested that both the pH and PNH content played important roles in the drug release behaviors of the hydrogels.     

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.     

Dual‐responsive semi‐interpenetrating network beads based on calcium alginate/poly(N‐isopropylacrylamide)/poly(sodium acrylate) for sustained drug release

To improve the mechanical strength of natural hydrogels and to obtain a sustained drug‐delivery device, temperature‐/pH‐sensitive hydrogel beads composed of calcium alginate (Ca‐alginate) and poly(N‐isopropylacrylamide) (PNIPAAm) were prepared in the presence of poly(sodium acrylate) (PAANa) with ultrahigh molecular weight (M_η ≥ 1.0 × 10⁷) as a strengthening agent. The influence of PAANa content on the properties, including the beads stability, swelling, and drug‐release behaviors, of the hydrogels was evaluated. Scanning electron microscopy and oscillation experiments were used to analyze the structure and mechanical stability of the hydrogel beads, respectively. The results show that stability of the obtained Ca‐alginate/PNIPAAm hydrogel beads strengthened by PAANa the alginate/poly(N‐isopropyl acrylamide) hydrogel bead (SANBs) was significantly improved compared to that of the beads without PAANa (NANBs) at pH 7.4. The swelling behavior and drug‐release capability of the SANBs were markedly dependent on the PAANa content and on the environmental temperature and pH. The bead sample with a higher percentage of PAANa exhibited a lower swelling rate and slower drug release. The drug release profiles from SANBs were further studied in simulated intestinal fluid, and the results demonstrated here suggest that SANBs could serve as a potential candidate for controlled drug delivery in vivo. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

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     

Network structure and temperature dependence swelling behavior of PEG-b-Poly (NIPAM-co-AMPSA) hydrogels in water

Temperature sensitive hydrogels were prepared by free radical polymerization of N-isopropylacrylamide (NIPAM) and 2-acrylamido-2-methylpropanesulphonic acid (AMPSA) in presence of polyethylene glycol (PEG) as macroinitiator. The aim of the work reported here was to investigate temperature sensitive swelling and deswelling behaviors of the hydrogels in water in order to investigate the effect of various amounts of AMPSA. The result indicated that the incorporation of a hydrophilic ionizable comonomer (AMPSA) affects the temperature sensitivity, swelling/deswelling, morphology and network structure of the hydrogels. The volume fraction in the swollen state (V_2m), the number average molecular weight between cross-links ([`(M)]_c {\overline M_c} ), the number of segments between the cross-linked point (N), polymer-solvent interaction parameter (χ), enthalpy (ΔH) and entropy (ΔS) were determined using the Flory-Rehner theory at equilibrium swelling. The negative values of ΔH and ΔS showed that the prepared hydrogels had lower critical solution temperature (LCST). The Flory-Rehner theory of swelling equilibrium was qualitatively satisfied with the experimental data of hydrogels at different temperature.     

Preparation and characterization of pH-sensitive,interpenetrating networks of poly(vinyl alcohol) and poly(acrylic acid)

Hydrogels with varying cross-linking ratio and ionic content were prepared from interpenetrating networks of poly(vinyl alcohol) and poly(acrylic acid). Equilibrium swelling studies were conducted and the average molecular weight between cross-links, M _c, and mesh size were determined. Hydrogels with large M _c, values were found to swell to a greater extent than those with small M _c values. It was also observed that an increase in M _c yielded faster swelling and deswelling rates, as the rates for membranes with M _c = 18,000 were about twice as fast as were the rates for membranes with M _c = 34,000. Oscillatory swelling behavior was investigated in response to changes in the pH and ionic strength of the swelling medium. A change in pH from 3 to 6 caused an ionization of the hydrogels and an increase in the weight swelling ratio, with a greater increase exhibited by IPNs with a higher ionic content. Increase in pH also caused an increase in the average mesh size. © 1995 John Wiley & Sons, Inc.     

Effects of oxidant and dopants on the properties of cellulose/PPy conductive composite hydrogels

Cellulose/Polypyrrole (PPy) composite hydrogels were prepared by in situ chemically oxidative polymerization of pyrrole in the cellulose matrix. Ferric chloride (FeCl₃) was used as an oxidant and four sulfonic compounds were used as dopants in order to investigate the effects on the properties of cellulose/PPy conductive composite hydrogels. The extent of polymerization of PPy was determined by the amount of the oxidant and the composite hydrogels with oxidant at 0.3M?0.5M exhibited the higher conductivities for the intrachain and interchain conductivities of conductive polymers; the fracture stress of the composite hydrogels could be up to 26.25 MPa with a strain of 86.8% when the oxidant was at 0.5M. Doping is an efficient way to improve the conductivity of the composite hydrogels and four kinds of dopant were compared in this work. Long alkane chain and side group in dopants can increase the steric hindrance of PPy polymerization which resulted in the lower conductivity of the composite hydrogels compared to dopants with smaller steric hindrance. The conductivity of the composite hydrogel firstly increased and then decreased with the concentration of dopants from 0.1M to 1.0M in this work. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43759.     

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     

Poly(vinyl alcohol)/chitosan/honey/clay responsive nanocomposite hydrogel wound dressing

Many efforts have been made to develop modern wound dressings to overcome limitations of traditional ones. Smart nanocomposite hydrogels are appropriate candidates. In this work, a novel responsive nanocomposite hydrogel based on poly(vinyl alcohol)/chitosan/honey/clay was developed and evaluated as a novel wound dressing. The morphology and properties of synthesized nanocomposite hydrogels loaded with honey as a drug model were investigated. The exfoliated morphology of nanocomposite was confirmed by X‐ray diffractometry. Swelling studies were performed at 20 and 37 °C at various pH. The results showed that swelling increased as a result of temperature rise and maximum swelling occurred at a pH of 2. In vitro release of honey was also studied at the same conditions. Corresponding results indicated faster honey release rate at higher pH values. MTT results exhibited no cytotoxicity in nanocomposite hydrogel system. Investigation of antibacterial activity revealed more than 99% antibacterial activity for proposed system. In vivo results confirmed the wound healing ability of developed system. Generally, appropriate properties of proposed system made it ideal in wound dressing applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46311.     

Removal of Hg(II) from acid aqueous solutions by poly(N‐vinylimidazole) hydrogel

Caption of Hg(II) from acid aqueous solution by immersed poly(N‐vinylimidazole) hydrogel particles was studied as a function of pH, counterion, and cation concentration. Fitting parameters to several sorption isotherms have been determined. Their values depend mostly on pH and less, on temperature and counterion, and suggest a large affinity of imidazole groups in the gel and mercury cations. Practically total removal (94.4%) of Hg(II) is achieved at pH = 2, with 10 g of dry gel per liter of solution, when cation concentration was as large as 15,000 ppm (0.075 M). Polymer protonation decreases about fourfold the cation affinity, supporting competitive protonation‐complexation mechanisms. By its side, metal uptake decreases polymer protonation. Thermal stability of loaded gels decreases with respect to metal free hydrogels. Scanning electron micrographs reveal no changes in the gel morphology upon cation binding, but T_g increases significantly with the Hg(II) content of loaded gels and swelling decreases moderately, indicating the role of the cation as ionic crosslinker. Practically total elution of Hg(II) is achieved with 1 M HNO₃ in consecutive loading‐elution cycles. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1467–1475, 2001     

Kinetic degradation and controlled drug delivery system studies for sensitive hydrogels prepared by gamma irradiation

Ternary mixtures of N‐vinyl‐2‐pyrrolidone/itaconic acid and gelatin were irradiated by gamma rays at 30 kGy/s and at ambient temperature to prepared poly (NVP/IA and G) hydrogels. Poly (NVP/IA) hydrogels were prepared in different compositions (NVP/IA) mole ratio, (100/0), (98/1.5), (96.5/3.5), and (93/7.0) at 30 kGy. Then adding gelatin at different content (5, 10, 15, 20) mg to the best composition (NVP/IA/H₂O) (93/7)% for the characterization of network structure of these hydrogels, kinetic swelling drug release behavior and Scan Electron Microscope was studied. The equilibrium degree of swelling for P(NVP/IA) and P(NVP/IA/G) copolymer and the swelling‐degradation kinetics were also studies. According to dynamic swelling studies, both the diffusion exponent and the diffusion coefficient increase with increasing content of (IA), whereas, the addition of gelatin to (NVP/IA) composition by different content did not lead to any significant change in swelling percent. Also, the swelling behavior of copolymer hydrogels in response to pH value of the external media was studied, it is noted that the highest swelling values were at pH 4. The in vitro drug release behavior of these hydrogels was examined by quantification analysis with a UV/VIS spectrophotometers. Chlorpromazine hydrochloride was loaded into dried hydrogels to investigate the stimuli‐sensitive property at the specific pH and the drug release profile of these pH‐sensitive hydrogels in vitro. The release studies show that the highest value of release was at pH 4 which can be used for drug delivery system. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Photo‐cross‐linked biodegradable thermo‐ and pH‐responsive hydrogels for controlled drug release

A new strategy was developed to prepare thermo‐ and pH‐sensitive hydrogels by the crosslinking of poly(N‐isopropylacrylamide) with a biodegradable crosslinker derived from poly(L ‐glutamic acid). Hydrogels were fabricated by exposing aqueous solutions of precursor containing photoinitiator to UV light irradiation. The swelling behaviors of hydrogels at different temperatures, pHs, and ionic strengths were examined. The hydrogels shrank under acidic condition or at temperature above their collapse temperature and would swell in neutral or basic media or at lower temperature. These processes were reversible as the pH or temperature changed. All hydrogels exhibited no weight loss in the simulated gastric fluid but degraded rapidly in the simulated intestinal condition. Bovine serum albumin were used as a model protein drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and temperatures. The pH and temperature dependent release behaviors indicated the promising application of these materials as stimuli‐responsive drug delivery vehicles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Release of vitamin B12 from poly(N‐vinyl‐2‐pyrrolidone)‐crosslinked polyacrylamide hydrogels: A kinetic study

Hydrogels, composed of poly(N‐vinyl‐2‐pyrrolidone) and crosslinked polyacrylamide, were synthesized and the release of vitamin B₁₂ from these hydrogels was studied as a function of the degree of crosslinking and pH of the external swelling media. The three drug‐loaded hydrogel samples synthesized with different crosslinking ratios of 0.3, 0.7, and 1.2 (in mol %) follow different drug‐release mechanisms, that is, chain relaxation with zero‐order, non‐Fickian and Fickian, or diffusion‐controlled mechanisms. To establish a correlation between their swelling behavior and drug‐release mechanism, the former was studied by the weight‐gain method and, at the same time, the concentration of the drug released was studied colorimetrically. Various swelling parameters such as the swelling exponent n, gel‐characteristic constant k, penetration velocity v, and diffusion coefficient D were evaluated to reflect the quantitative aspect of the swelling behavior of these hydrogels. Finally, the drug‐release behavior of the hydrogels was explained by proposing the swelling‐dependent mechanism. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1706–1714, 2000     

Dynamic swelling behavior of pH‐sensitive anionic hydrogels used for protein delivery

There have been many attempts to use anionic hydrogels as oral protein delivery carriers because of their pH‐responsive swelling behavior. The dynamic swelling behavior of poly(methacrylic acid‐co‐methacryloxyethyl glucoside) and poly(methacrylic acid‐g‐ethylene glycol) hydrogels was investigated to determine the mechanism of water transport through these anionic hydrogels. The exponential relation M_t/M_∞ = ktⁿ (where M_t is the mass of water absorbed at time t and M_∞ is the mass of water absorbed at equilibrium) was used to calculate the exponent (n) describing the Fickian or non‐Fickian behavior of swelling polymer networks. The mechanism of water transport through these gels was significantly affected by the pH of the swelling medium. The mechanism of water transport became more relaxation‐controlled in a swelling medium of pH 7.0, which was higher than pK_a of the gels. The experimental results of the time‐dependent swelling behaviors of the gels were analyzed with several mathematical models. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1606–1613, 2003