Immobilization of 2,5‐dimethyl‐4‐benzoyl‐oxypiperidine succinate over polyacrylic acid (PAA) gels. II. Study of quantitative characteristics of immobilization of succinate of 2,5‐dimethyl‐4‐benzoyl‐oxypiperidine over PAA

By use of a spectrophotometric method the quantity of binding of medicinal compound [succinate of 2,5‐dimethyl‐4‐benzoyl‐oxypiperidine (AK‐29)], over gels of polyacrylic acid, and liberation of medicinal compound (MC) from the gel phase were investigated. It was established that both concentration and pH dependency of AK‐29 sorption over PAA gels pass through a maximum and increase with increasing degree of gel crosslinking. The yield of MC from the gel phase, depending on the conditions, reaches 80% and accelerates at the change of the aqueous phase to a physiological one. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1187–1192, 2005     

Mechanical properties of poly(N‐isopropyl‐acrylamide‐co‐itaconic acid) hydrogels

Hydrogels of N‐isopropylacrylamide and itaconic acid were synthesized with different monomer ratios and with two crosslinking agent concentrations. The different xerogels were immersed in water and the swelling process was conducted up to equilibrium conditions at two temperatures (22 and 37°C). These temperatures are lower and higher than the transition temperature shown by PNIPA hydrogels. The mechanical properties of the different solvated hydrogels were examined by oscillatory shear measurements at 22 and 37°C. The copolymer volume fraction and the elastic storage modulus of the hydrogels decreased as the itaconic acid percentage in the copolymer increased. This behavior was attributed to the higher hydrophilic character of the itaconic acid comonomer. Effective crosslinking density, molar mass between crosslinks, and the polymer–solvent interaction parameter were determined from the experimental values of the elastic storage moduli and the copolymer volume fractions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2540–2545, 2002     

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

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

Determination of average molecular weight between crosslinks and polymer–solvent interaction parameters of poly(acrylamide‐g‐ethylene diamine tetraacetic acid) polyelectrolyte hydrogels

Hydrogels containing tetraprotic acid moieties sensitive to pH changes of the swelling medium were prepared from the ternary systems acrylamide/ethylene diamine tetraacetic acid/water by irradiation with γ‐rays at ambient temperature. Gel compositions of poly(acrylamide‐g‐ethylene diamine tetraacetic acid) [P(AAm‐g‐EDTA)] hydrogels were determined by using a differential pulse polarography technique. Equilibrium swelling behavior of these hydrogels was studied using an equation, based on the Flory–Huggins thermodynamic theory, the phantom network theory of James–Guth, and the approaches of Brannon‐Peppas and Peppas, which was modified by the authors for determination of M _c and χ parameters. The equation modified by the authors for the determination of M _c and χ parameters were observed to describe very well the swelling behavior of the charged polymeric network. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2168–2175, 2004     

Synthesis and gelation of novel fluoroalkyl end‐capped N‐(1,1‐dimethyl‐3‐oxobutyl)acrylamide copolymers containing triol segments—Interaction of these fluorinated gels with various hydrophilic compounds

Fluoroalkyl end‐capped N‐(1,1‐dimethyl‐3‐oxobutyl)acrylamide (DOBAA) copolymers containing triol segments were prepared by the reactions of fluoroalkanoyl peroxide with the corresponding monomer and N‐tris(hydroxymethyl)methylacrylamide (NAT). These obtained fluorinated copolymers [R_F‐(DOBAA)_x‐(NAT)_y‐R_F] were found to cause gelation in water, dimethyl sulfoxide, and N,N‐dimethylformamide under the non‐crosslinked conditions, although the corresponding nonfluorinated DOBAA–NAT copolymer [‐(DOBAA)_x‐(NAT)_y‐] could cause no gelation in these solvents. This gelation is governed by the synergistic interaction of strong aggregations of end‐capped fluoroalkyl segments and intermolecular hydrogen bonding between triol segments. We also studied the uptake and release of a variety of hydrophilic compounds such as methylene blue, methyl orange, 4‐hydroxyazobenzene‐4′‐sulfonic acid sodium salt, 2,4‐dihydroxyazobenzene‐4′‐sulfonic acid sodium salt, acriflavine hydrochloride, acridine hydrochloride, lucigenin, and fluorescein by this fluorinated copolymer gel and fluoroalkyl end‐capped NAT homopolymer gel [R_F‐(NAT)_n‐RF] for comparison. It was demonstrated that the uptake and release ratios of these hydrophilic compounds by R_F‐(DOBAA)_x‐(NAT)_y‐R_F gel become generally lower than those of R_F‐(NAT)_n‐R_F gel. Interestingly, R_F‐(DOBAA)_x‐(NAT)_y‐R_F gel has no releasing power toward methylene blue, acridine hydrochloride, lucigenin, and fluorescein, although R_F‐(NAT)_n‐R_F gel has a good releasing power toward these compounds. Additionally, R_F‐(DOBAA)_x‐(NAT)_y‐R_F gel was applied to the controlled release of anticancer drugs such as methotrexate (MTX), and the releasing ratios of MTX became higher with increasing pH values (from pH 4.3 to 9.1). © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88:3212–3217, 2003     

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     

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

pH‐sensitive nanogels (NGs) based on poly(aspartic acid‐graft‐imidazole)‐poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH‐sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH‐sensitive NGs was studied using a model drug, irinotecan (IRI). IRI‐loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH‐dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH‐sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling–shrinkage. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46268.     

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.     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

γ‐Irradiation preparation of poly(acrylic acid)–chitosan hydrogels for in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a γ‐irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid (AAc) content increased. The equilibrium swelling studies of hydrogels prepared under various conditions were carried out in an aqueous solution, and the pH sensitivity in a range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30 kGy dose of radiation. In addition, an increase of the degree of swelling with an increase in the pH was noticed and it had the highest value at pH 12. The drug 5‐fluorouracil was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at intestinal pH and the rest of the drug was released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3270–3277, 2003     

Synthesis and characterization of novel pH‐responsive poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) hydrogels for drug delivery

In this study, N‐allylsuccinamic acid (NASA) was synthesized in a single step with a yield of 85%. Carboxylic acid containing NASA was characterized through Fourier transform infrared (FTIR) radiation and ¹H‐NMR and ¹³C‐NMR analysis, and then it was used for synthesis of poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) [p(HEMA‐co‐NASA)] hydrogels. The structure of the obtained pH‐responsive p(HEMA‐co‐NASA) hydrogels were characterized with FTIR spectroscopy and scanning electron microscopy analysis, and their swelling characterization was carried out under different drug‐release conditions. In the application step of the study, the hydrogels were used for the in vitro release of vitamin B12 and Rhodamine 6G, which were selected as model drugs. We determined that the hydrogels used as a drug‐delivery matrix could release the drug they had absorbed under different release conditions (phosphate‐buffered saline, 0.9% NaCl, and pH 1.2) at high rates for time periods of up to 24 h. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39660.     

Fluconazole release through semi‐interpenetrating polymer network hydrogels based on chitosan,acrylic acid,and citraconic acid

Semi‐interpenetrating polymer network hydrogels with different compositions of chitosan (Cs), acrylic acid, and citraconic acid were synthesized via free‐radical polymerization with ethylene glycol dimethacrylate as a crosslinker. The variations of the swelling percentages of the hydrogels with time, temperature, and pH were determined, and Cs–poly(acrylic acid) (PAA) hydrogels were found to be most swollen at pH 7.4 and 37°C. Scanning electron micrographs of Cs–PAA and Cs–P(AA‐co‐CA)‐1 (Cs‐poly(acrylicacid‐co‐citraconir acid)^?1) were taken to observe the morphological differences in the hydrogels. Although the less swollen hydrogel, Cs–P(AA‐co‐CA)‐1, had a sponge‐type structure, the most swollen hydrogel, Cs–PAA, displayed a uniform porous appearance. Fluconazole was entrapped in Cs–P(AA‐co‐CA)‐1 and Cs–PAA hydrogels, and the release was investigated at pH 4.0 and 37°C. The kinetic release parameters of the hydrogels (the gel characteristic constant and the swelling exponent) were calculated, and non‐Fickian diffusion was established for Cs–PAA, which released fluconazole much more slowly than the Cs–P(AA‐co‐CA)‐1 hydrogel. A therapeutic range was reached at close to 1 h for both hydrogels. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and characterization of polyacrylic acid‐poly(vinyl alcohol)‐based interpenetrating hydrogels

Some structural features of hydrogels from poly(acrylic acid) (PAAc) of various crosslinking degrees have been investigated through mechanical and swelling measurements. Interpenetrating polymer hydrogels (IPHs) of poly(vinyl alcohol) (PVA) and PAAc have been prepared by a sequential method: crosslinked PAAc chains were formed in aqueous solution by crosslinking copolymerization of acrylic acid and N,N‐methylenebisacrylamide in the presence of PVA. The application of freeze–thaw (F–T) cycles leads to the formation of a PVA hydrogel within the synthesized PAAc hydrogel. The swelling and viscoelastic properties of the IPHs were evaluated as a function of the content of crosslinker and the application of one F–T cycle. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5789–5794, 2006     

Interpenetrating polymer networks of poly(butyl methacrylate) and poly(α‐terpineol‐co‐styrene): Synthesis and characterization

Simultaneous interpenetrating polymer networks (IPNs) based on poly(butyl methacrylate) and poly(α‐terpineol‐co‐styrene) were synthesized with azobisisobutyronitrile (AIBN) as the initiator and divinyl benzene as the crosslinking agent in xylene under an inert nitrogen atmosphere. Fourier transform infrared spectra provided structural evidence for the IPNs, indicating characteristic frequencies of ester groups of butyl methacrylate at 1723 cm^?1 and alcoholic groups of α‐terpineol at 3436 cm^?1. Scanning electron microscopy revealed threadlike network structures. Properties such as percentage swelling and average molecular weight between crosslinks were direct functions of the copolymer and initiator (AIBN) concentrations and inverse functions of the monomer (butyl methacrylate) and crosslinking agent (divinyl benzene) concentrations. Differential scanning calorimetry showed an IPN glass‐transition temperature at 80.2°C. The thermal decompositions of the IPNs were established with the help of thermogravimetric analysis. The value of the activation energy, calculated from thermogravimetric analysis with the Coats and Redfern equation, was 23 kJ/mol. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 343–352, 2006     

Oxaliplatin‐loaded crosslinked polymeric network of chondroitin sulfate‐co‐poly(methacrylic acid) for colorectal cancer: Its toxicological evaluation

The purpose of this study was to develop and characterize chemically crosslinked chondroitin sulfate‐co‐poly(methacrylic acid) (CSMA) hydrogels for colon targeting of oxaliplatin (OXP) to treat colorectal cancer. CSMA hydrogels were synthesized by free‐radical polymerization. Chondroitin sulfate was chemically crosslinked with methacrylic acid in an aqueous medium. Ammonium peroxodisulfate and N,N‐methylene bisacrylamide were used as the initiator and crosslinker, respectively. Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, X‐ray diffraction, and scanning electron microscopy studies were performed to characterize the fabricated polymeric system. The pH‐sensitive characteristics of the hydrogels were evaluated by swelling dynamics and equilibrium swelling ratio measurements at pH 1.2 and 7.4. A toxicity study of the developed formulations was also conducted on rabbits to determine the toxicity of the drug‐carrier system to the biological system. The characterization studies confirmed the formation of a new polymeric network. A high OXP loading and higher drug release was observed at pH 7.4. The toxicity study confirmed that the developed formulations were nontoxic to the biological system. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45312.     

Stability of DL‐poly(lactic acid) in aqueous solutions

DL ‐poly(lactic acid) of molecular weight about 2500 was prepared by polycondensation of lactic acid and characterized by viscosimetry, infrared spectroscopy, light scattering, GPC, and NMR. Tablets made of the above polymer were immersed in buffer solutions at 37°C, and their swelling behavior was recorded as a function of time, in terms of weight gain. In the same experiments, the hydrolytic stability of PLA was assessed by measuring the weight loss after drying the tablets. To inhibit any degradation due to bacteria, formaldehyde was added to the solution as a biostatic factor. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 795–804, 2003     

Modified carrageenan. 4. Synthesis and swelling behavior of crosslinked κC‐g‐AMPS superabsorbent hydrogel with antisalt and pH‐responsiveness properties

To synthesize a novel biopolymer‐based superabsorbent hydrogel, 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) was grafted onto kappa‐carrageenan (κC) backbones. The graft copolymerization reaction was carried out in a homogeneous medium and in the presence of ammonium persulfate (APS) as an initiator, N,N,N′,N′‐tetramethyl ethylenediamine (TMEDA) as an accelerator, and N,N′‐methylene bisacrylamide (MBA) as a crosslinker. A proposed mechanism for κC‐g‐AMPS formation was suggested and the hydrogel structure was confirmed using FTIR spectroscopy. The affecting variables on swelling capacity, i.e., the initiator, the crosslinker, and the monomer concentration, as well as reaction temperature, were systematically optimized. The swelling measurements of the hydrogels were conducted in aqueous solutions of LiCl, NaCl, KCl, MgCl₂, CaCl₂, SrCl₂, BaCl₂, and AlCl₃. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as antisalt superabsorbents. The swelling of superabsorbing hydrogels was measured in solutions with pH ranging 1 to 13. The κC‐g‐AMPS hydrogel exhibited a pH‐responsiveness character so that a swelling–deswelling pulsatile behavior was recorded at pH 2 and 8. The overall activation energy for the graft copolymerization reaction was found to be 14.6 kJ/mol. The swelling kinetics of the hydrogels was preliminarily investigated as well. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 255–263, 2005     

Temperature and pH‐response swelling behavior of poly(2‐ethyl‐2‐oxazoline)/chitosan interpenetrating polymer network hydrogels

Interpenetrating polymer network (IPN) hydrogels composed of poly(2‐ethyl‐2‐oxazoline) (PEtOz) and chitosan (CS) were prepared with radical polymerization and were characterized for their swelling properties. Sample OC11 (hydrogel weight ratio PEtOz/CS = 1/1) swelled more than samples OC21 (PEtOz/CS = 2/1) and OC31 (PEtOz/CS =3/1), exhibiting a swelling ratio of about 2000 wt % in deionized water; the swelling ratios of the other samples were about 1000 and 700 wt %. The swelling behavior of the IPN hydrogels was observed under various pH and temperature conditions. The swelling ratios of the samples ranged from about 2000 to 6500 wt % at lower pHs, with a maximum swelling ratio of about 6500 wt % in a pH 2 aqueous solution. They exhibited low critical solution temperature behavior, with sample OC31 more sensitive to temperature and sample OC11 more sensitive to pH. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1100–1103, 2006     

Kinetic analysis of the swelling behavior of poly(n‐butylacrylate‐1,6‐hexanedioldiacrylate) networks in 4‐cyano‐4′‐n‐pentyl‐biphenyl (5CB)

The dynamic swelling behavior of chemically crosslinked poly(n‐butylacrylate/1,6‐hexanedioldiacrylate) [poly(Abu‐HDDA)] networks, immersed in an nematogenic and two isotropic solvents, was experimentally analyzed. These networks were elaborated by ultraviolet (UV)–visible light‐induced radical polymerization/crosslinking reactions of Abu/HDDA mixtures, to yield poly(Abu/0.5 wt % HDDA) and poly(Abu/5 wt % HDDA) networks corresponding to weakly and strongly crosslinked systems, respectively. The swelling behavior of these poly(Abu‐HDDA) networks was investigated by immersion in excess solvent, followed by subsequent measurements of the variation of the sample size by means of optical microscopy, depending on temperature and immersion time. Methanol and toluene were employed as isotropic solvents and the nematic liquid crystal molecule 4‐cyano‐4 ′ ‐n‐pentyl‐biphenyl, was considered as anisotropic medium. Swelling ratios were calculated by taking into account diameter sizes as function of immersion time compared to the dry state. Experimental data were analyzed using the Komori–Sakamoto approach and the results of this model were found to be in good agreement with the obtained data. The plateau values of the swelling curves at equilibrium were used to establish phase diagrams as function of temperature and solvent concentration. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45452.