Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation

The new copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were prepared by gamma irradiation, in order to examine the potential use of these hydrogels in controlled drug release systems. The influence of IA content in the gel on the swelling characteristics and the releasing behavior of hydrogels, and the effect of different drugs, theophylline (TPH) and fenethylline hydrochloride (FE), on the releasing behavior of P(HEMA/IA) matrix were investigated in vitro. The diffusion exponents for swelling and drug release indicate that the mechanisms of buffer uptake and drug release are governed by Fickian diffusion. The swelling kinetics and, therefore, the release rate depends on the matrix swelling degree. The drug release was faster for copolymeric hydrogels with a higher content of itaconic acid. Furthermore, the drug release for TPH as model drug was faster due to a smaller molecular size and a weaker interaction of the TPH molecules with(in) the P(HEMA/IA) copolymeric networks.     

Swelling behaviors, tensile properties and thermodynamic studies of water sorption of 2-hydroxyethyl methacrylate/epoxy methacrylate copolymeric hydrogels

A series of copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and epoxy methacrylate (EMA) were synthesized by bulk polymerization. Swelling behaviors and tensile properties of hydrogels were studied. Dynamic swelling behaviors of copolymeric hydrogels indicate that the swelling process of these polymers follows Fickian behavior. The equilibrium water content (EWC) decreased and volume fraction of polymer in hydrogel (?₂) increased with EMA content increasing due to its hydrophobicity. The increase of ionic strength of swelling medium or temperature results in a decrease in EWC and an increase in values of ?₂. Young’s modulus and tensile strength of hydrogels, as well as effective crosslink density (v_e), increased as EMA content increased or ionic strength of swelling medium increased, attributing to increasing interaction between hydrophobic groups and polymer-polymer interaction with an increase in EMA content or in ionic strength. The polymer-solvent interaction parameter χ reflecting thermodynamic interaction was also studied. As EMA content, ionic strength of swelling medium or temperature increased, the values of χ increased. The values of χ and its two components χ_H and χ_S varied with increasing T. The negative values and trend of the enthalpy and entropy of dilution derived from values of χ_S and χ_H, could be explained on the basis of structuring of water through improved hydrogen bonding and hydrophobic interaction.     

Smart poly(2-hydroxyethyl methacrylate/itaconic acid) hydrogels for biomedical application

pH- and temperature-sensitive hydrogels, based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) copolymers, were prepared by γ-irradiation and characterized in order to examine their potential use in biomedical applications. The influence of comonomer ratio in these smart copolymers on their morphology, mechanical and thermal properties, biocompatibility and microbe penetration capability was investigated. The mechanical properties of copolymers were investigated using the dynamic mechanical analysis (DMA), while their thermal properties and morphology were examined by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The morphology, mechanical and thermal properties of these hydrogels were found to be suitable for most requirements of biomedical applications. The in vitro study of P(HEMA/IA) biocompatibility showed no evidence of cell toxicity nor any considerable hemolytic activity. Furthermore, the microbe penetration test showed that neither Staphylococcus aureus nor Escherichia coli passed through the hydogel dressing; thus the P(HEMA/IA) dressing could be considered a good barrier against microbes. All results indicate that stimuli-responsive P(HEMA/IA) hydrogels have great potential for biomedical applications, especially for skin treatment and wound dressings.     

Thermodynamic properties of copolymeric hydrogels based on 2-hydroxyethyl methacrylate and a zwitterionic methacrylate

The copolymerisation of 2-hydroxyethyl methacrylate and a zwitterionic methacrylate, namelyN,N-dimethyl-N-methacryloxyethyl-N-(3-sulphopropyl)-ammonium betaine (SPE), in the presence of a tetrafunctional crosslinker has been effected to 100% conversion by -irradiation. The resultant xerogels of different compositions were swollen to equilibrium in water to yield hydrogels. Volumetric swelling and compression-strain measurements were made over the temperature range 278–343 K. All these copolymers showed an increasing volumetric swelling with temperature, but the derived values of the partial molar enthalpy, entropy and Gibbs free energy of dilution showed certain differences which were interpreted on the basis of copolymer dyad distribution.     

Swelling studies of copolymeric acrylamide/crotonic acid hydrogels as carriers for agricultural uses

In this study, highly swollen acrylamide/crotonic acid hydrogels (in a rod form) containing some inorganic salts such as ammonium nitrate, potassium nitrate and ammonium sulphate used as fertilizer, an agricultural drug such as Dalapon (sodium 2,2‐dichloropropionate) and two crosslinkers such as ethylene glycol dimethacrylate and 1,4‐butandiol dimethacrylate were prepared by copolymerization of acrylamide and crotonic acid with γ‐radiation. As a result of swelling tests, the influence of γ‐ray dose and relative content of crotonic acid on the swelling properties, the diffusional behavior of water, diffusion coefficients and network properties of the hydrogel systems were examined. Acrylamide/crotonic acid hydrogels containing these salts and agricultural drug were swollen in the range 2045–400% in water, while polyacrylamide hydrogels swelled in the range 660–700%. Water intake of hydrogels followed a nonFickian‐type diffusion. Copyright © 2000 John Wiley & Sons, Ltd.     

Anticancer drug release from poly(N-isopropylacrylamide/itaconic acid) copolymeric hydrogels

The drug uptake and release of anticancer drug from N-isopropylacrylamide/itaconic acid copolymeric hydrogels containing 0–3 mol% of itaconic acid irradiated at 48 kGy have been investigated. 5-Fluorouracil (5-FU) is used as a model anticancer drug. The effect of 5-FU solution on swelling characteristics of PNIPAAm and P(NIPAAm/IA) copolymeric hydrogels have also been studied. The percent swelling, equilibrium swelling, equilibrium water/5-FU content and diffusion constant values are evaluated for poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-isopropylacrylamide/itaconic) (P(NIPAAm/IA)) hydrogels at 130 ppm of 5-FU solution at room temperature. Diffusion of 5-FU solution into the hydrogels has been found to be the non-Fickian type. Finally, the kinetics of drug release from the hydrogels are examined.     

Radiation-induced synthesis and swelling properties of p(2-hydroxyethyl methacrylate/itaconic acid/oligo (ethylene glycol) acrylate) terpolymeric hydrogels

Since it is presumed that by incorporation of pH-responsive (IA) and temperature-responsive (OEGA) co-monomers, it is possible to prepare P(HEMA/IA/OEGA) hydrogels with dual (pH and thermo) responsiveness, the main purpose of our study is to investigate the influence of different mole fractions of IA and especially OEGA on the diversity of the swelling properties of the obtained hydrogels. For that reason, a series of terpolymeric hydrogels with different mole ratios of 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA) and oligo(ethylene glycol) acrylates (OEGA) was synthesised by gamma radiation. The obtained hydrogels were characterised by swelling studies in the wide pH (2.2–9.0) and temperature range (20–70 °C), confirming dual (pH and thermo) responsiveness and a large variation in the swelling capability. It was observed that the equilibrium swelling of P(HEMA/IA/OEGA) hydrogels, for a constant amount of IA, increased progressively with an increase in OEGA share. On the other hand, the dissociation of carboxyl groups from IA occurs at pH>4; therefore, small mole fractions of IA render good pH sensitivity and a large increase in the swelling capacity of these hydrogels at higher pH values. Additional characterisation of structure and properties was conducted by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and mechanical measurements, confirming that the inherent properties of P(HEMA/IA/OEGA) hydrogels can be significantly tuned by variation in their composition. According to all presented, it seems that the obtained hydrogels can be a beneficial synergetic combination for controlled delivery of bioactive molecules such as drugs, peptides, proteins, etc.     

Cationic dye adsorption by poly(N-isopropylacrylamide/maleic acid) copolymeric hydrogels prepared by gamma rays

N-isopropylacrylamide/maleic acid hydrogels containing different quantities of maleic acid have been synthesized with γ-radiation. The hydrogels were used in experiments on swelling, diffusion and adsorption of a cationic dye methylene blue. The diffusion of MB into the hydrogels was found to be the non-Fickian type. The factors influencing adsorption capacity of the hydrogel such as gel composition, and irradiation dose were systematically investigated. The equilibrium data for dye adsorption was better described by the Freundlich isotherm than Langmuir isotherm model. The kinetic studies showed that the pseudo-second-order kinetic model fits better than the data obtained from pseudo-first-order model.     

Uranyl ion uptake capacity of poly (N-isopropylacrylamide/maleic acid) copolymeric hydrogels prepared by gamma rays

The effect of gel composition, absorbed dose and pH of the solution on the uranyl ion uptake capacity of N-isopropylacrylamide/maleic acid copolymeric hydrogels containing 0–3 mol% of maleic acid at 48 kGy have been investigated. Uranyl uptake capacity of hydrogels are found to increase from 18.5 to 94.8 mg [UO₂²⁺]/g dry gel as the mole % of maleic acid content in the gel structure increased from 0 to 3. The percent swelling, equilibrium swelling and diffusion coefficient values have been evaluated for poly(N-isopropylacrylamide/maleic acid) hydrogels at 500 ppm of uranyl nitrate solution.     

Water diffusion in methacrylate based copolymer hydrogels of 2-hydroxyethyl methacrylate

The diffusion of water into cylinders of polyHEMA and copolymers of HEMA with THFMA, BMA and CHMA were studied over a range of copolymer compositions. The diffusion of water into the polymers was found to follow a Fickian, or case I mechanism. The diffusion coefficients of water were determined from mass measurements and NMR imaging studies. They were found to vary from 1.7 ± 0.2 x 10⁻¹¹ m² s⁻¹ for polyHEMA at 37°C to lower values for the copolymers. The mass of water absorbed at equilibrium relative to the mass of dry polymer varied from 52-58 wt% for polyHEMA to lower values for the copolymers.     

Dynamic mechanical properties of poly(2-hydroxyethyl methacrylate) hydrogels

Homogeneous and heterogeneous poly(2-hydroxyethyl methacrylate) hydrogels were prepared by copolymerization of 2-hydroxyethyl methacrylate and small amounts of ethylene glycol dimethacrylate in the presence of water; concentrations of water (V₁) in the polymerization mixture and the volume fractions of water (v₁) of the gels swollen to equilibrium were 40, 50, 60, 70% by volume, and 0.475, 0.541, 0.669, 0.778, respectively. From the homogeneous (clear) hydrogel (V₁ = 40%) preparation, four hydrogels were prepared with v₁ = 0.434, 0.418, 0.378, 0.326. Tensile dynamic moduli were measured in the frequency range from 0.006 to 0.6 cps and the temperature range from 0 to 40°C. In these cases, the influence of swelling on the shape of the relaxation spectra and on the monomeric unit friction coefficient was studied. The dependence of the friction coefficient on water concentration was interpreted in terms of free volume. In the heterogeneous (opaque) gel preparations (V₁ = 50, 60, 70%), the effect of the aqueous phase in the system on the mechanical behavior was described by a modification of the blending law of Ninomiya. For the systems with V₁ = 60% and 70% the shapes of the storage and loss moduli in the main transition region and the friction coefficient were similar to those of the homogeneous gel with V₁ = 40%, except for the decrease in absolute value of the storage moduli. For the system with V₁ = 50% the shape of the relaxation spectrum changes appreciably and the wedge distribution does not hold.     

Pore-size distributions of cationic 2-hydroxyethyl methacrylate (HEMA) hydrogels

Pore-size distributions have been measured for cationic 2-hydroxyethyl methacrylate (HEMA) hydrogels varying in cross-linker/monomer ratio and initial concentration of cationic comonomer MAPTAC, at swelling capacities ranging from 12 to 24 g swollen gel/g dry gel. Swelling capacities were measured at about 6 °C in pure water and in aqueous sodium-azide solutions ranging in concentration from 5 × 10⁻⁴ to 2 × 10⁻¹ M. The mixed-solute-exclusion method (introduced by Kuga) was used to obtain the experimental solute-exclusion curve, representing the amount of imbibed liquid inside the gel inaccessible to a solute of radius r. The pore-size distributions were obtained by using Casassa's Brownian-motion model and numerically solving the Fredholm integral equation. The pore-size distributions shift to higher mode values (57.8-60.9 Å) with decreasing initial cross-linker concentration at the same swelling capacity of about 12. Raising swelling capacities from 11.1 to 23.9 significantly increases the variance from 5.66 × 10³ to 2.67 × 10⁴ Ų. Changes in the concentration of the cationic comonomer MAPTAC do not significantly influence the pore-size distributions.     

Interaction of urea with poly(2-hydroxyethyl methacrylate) hydrogels

The interaction of poly(2-hydroxyethyl methacrylate) [poly(HEMA)] and other similar hydrogels with dilute urea solution has been studied by a variety of techniques, including swelling experiments, fluorescence quenching, near infrared spectroscopy and fundamental band infrared spectroscopy. The results obtained indicate that the anomalous swelling behavior of poly(HEMA) gels in the presence of such dilute urea solutions is probably not due to the disruption of a secondary hydrophobic bond structure as has been generally believed. Although poly(HEMA) gels do contain sites that can participate in hydrophobic bonding, the evidence gathered indicates that dilute urea solutions have no effect on such bonds. A plausible model that does fit all the data involves the interaction of urea with a secondary structure composed of hydrogen-bonded hydroxyl groups, stabilized by the exclusion of water molecules from the regions containing the bonds.     

Swelling behaviour of crosslinked hydrogels based on (2-hydroxyethyl methacrylate) with a zwitterionic comonomer (1-3-sulfopropyl-2-vinyl-pyridinium-betaine)

Copolymeric hydrogels were prepared by the chemically initiated free radical copolymerization in aqueous solution of mixtures of [1-(3-sulfopropyl)-2-vinyl-pyridinium-betaine] (SPV) and (2-hydroxyethyl methacrylate) (HEMA) in the presence of a crosslinking agent N,N′-methylene-bis-acrylamide (MBA). The hydrogels were swollen to equilibrium in water and aqueous KSCN at 298 K and their swelling behaviour has been investigated using gravimetric measurements. The effects of the concentration of KSCN and the mole fraction of SPV in the feed (F_s) have been noted and discussed. The main findings are:(a) In water, the water content (W₁) of copolymeric hydrogels is insensitive to SPV content at F_s ? 0.45. In contrast, W₁ decreases sharply with decreasing F_s within the range of 0 < F_s < 0.45. (b) In aq. KSCN, the degree of total swelling (W) exceeds the value in pure water, the enhancement in swelling being most marked at low values of [KSCN]. The content of water within the hydrogel increases with KSCN concentration in the swelling medium for low values of [KSCN], but thereafter falls with further increase in salt concentration. In contrast, the salt content within the swollen hydrogel displays a continuous increase with increasing [KSCN]. All these results of item (b) are for copolymeric hydrogels within the full range of F_s (0 < F_s < 1). (c) at a fixed aq. KSCN concentration, both W and W₁ increase sharply with increasing F_s over the entire range of copolymer composition.     

Swelling equilibria and dye adsorption studies of chemically crosslinked superabsorbent acrylamide/maleic acid hydrogels

Superswelling acrylamide (AAm)/maleic acid (MA) hydrogels were prepared by free radical polymerization in aqueous solution of AAm with MA as comonomer with some multifunctional crosslinkers such as trimethylolpropane triacrylate and 1,4-butanediol dimethacrylate. AAm/MA hydrogels were used in experiments on swelling and adsorption of a water-soluble monovalent cationic dye such as Basic Blue 17 (Toluidin Blue). As a result of dynamic swelling tests, the influence of relative content of MA on the swelling properties of the hydrogel systems was examined. AAm/MA hydrogels were swollen in the range 1660-6050% in water, while AAm hydrogels swelled in the range 780-1360%. Equilibrium water content of AAm/MA hydrogels were calculated in the range 0.8873-0.9837. Water intake of hydrogels followed a non-Fickian type diffusion. The uptake of the cationic dye, BB-17 to AAm/MA hydrogels is studied by batch adsorption technique at 25 °C. In the experiments of the adsorption equilibrium, S-type adsorption in Giles's classification system was found. The binding ratio of hydrogel/dye systems was gradually increased with the increase of MA content in the AAm/MA hydrogels.     

Investigation of drug release from thermo‐ and pH‐sensitive poly(N‐isopropylacrylamide/itaconic acid) copolymeric hydrogels

N‐Isopropylacrylamide/itaconic acid copolymeric hydrogels were prepared by irradiation of the ternary mixtures of N‐isopropylacrylamide/itaconic acid/water by γ‐rays at ambient temperature. The dependence of swelling properties and phase transitions on the comonomer concentration and temperature were investigated. The hydrogels showed both temperature and pH responses. The effect of comonomer concentration on the uptake and release behavior of the hydrogels was studied. Methylene blue (MB) was used as a model drug for the investigation of drug uptake and release behavior of the hydrogels. The release studies showed that the basic parameters affecting the drug release behavior of the hydrogels were pH and temperature of the solution. Copyright © 2004 John Wiley & Sons, Ltd.     

Dynamic deswelling studies of poly(N-vinyl-2-pyrrolidone/itaconic acid) hydrogels swollen in water and terbinafine hydrochloride solutions

Deswelling kinetics of water and terbinafine hydrochloride adsorbed poly(N-vinyl-2-pyrrolidone/itaconic acid) P(VP/IA) hydrogels were investigated. Hydrogels were prepared by irradiating the ternary mixture of VP/IA and cross-linking agent ethylene glycol dimethacrylate (EGDMA) in water by γ-rays at ambient temperature. Hydrogels swelled in pure water and terbinafine hydrochloride (TER-HCl) solutions at room temperature and deswelling or water loss were investigated between 4 and 45 °C temperature range and on human skin. The influence of IA content, % swelling, temperature and TER-HCl content on the water loss from gel matrix were investigated. Induction time for 80% water loss from hydrogel systems are found to increase from 9.6 to 21.2 h by increasing IA content in the gel system at 25 °C and decreased by 11 h with addition of TER-HCl in the gel system. Kinetic analyses had shown that the basic properties affecting the water loss behavior of these hydrogels are the IA and TER-HCl content and temperature of the medium.     

Swelling,elasticity and structure of hydrogels prepared via bis-macromonomers of poly(ethylene oxide)

The effect of swelling on the shear modulus was studied for hydrogels prepared by radical polymerization of methacrylate-terminated poly(ethylene oxide) (PEO) bis-macromonomers of different molecular weight. Gels made of long chains (M = 12000 or 6000) display classical softening upon swelling, whereas gels made of shorter chains (M = 4000 or 2000) remain rigid or even stiffen. The abnormal behaviour is explained by a specific character of network junctions presented by polymethacrylate chains in which each unit is linked with a PEO network chain. It is assumed that the interactions among densely grafted PEO chains result in their stretching on polymerization and non-affine deformation on swelling, which stiffen the gel. This is verified by the data on copolymer (macromonomers - 2-hydroxyethyl methacrylate) gels that have lesser densities of PEO chains attached to the junctions and show weaker stiffening on swelling. The osmotic pressure of gels was estimated from the swelling pressure and shear modulus. Similar to the mixing pressure of equivalent PEO solutions, it varies as the 9/4 power of polymer concentration. At the same time, it is lower than the mixing pressure. This indicates that the junctions make only quantitative changes in the osmotic properties of macromonomer chains.     

pH-thermoreversible hydrogels. I. Synthesis and characterization of poly(N-isopropylacrylamide/maleic acid) copolymeric hydrogels

N-isopropylacrylamide (NIPAAM)/maleic acid (MA) copolymeric hydrogels were prepared by irradiating the ternary mixtures of NIPAAM/MA/Water by γ-rays at ambient temperature. The influence of external stimuli such as pH and temperature of the swelling media on the equilibrium swelling properties was investigated. The hydrogels showed both temperature and pH responses. The effect of comonomer concentration and irradiation dose on the swelling equilibria and phase transition was studied. For the characterization of these hydrogels, the diffusion behaviour and molecular weight between crosslinks were investigated.