Investigation the correlation between chemical structure and swelling,thermal and flocculation properties of carboxymethylcellulose hydrogels

Hydrophilic polymer networks (hydrogels) based on sodium carboxymethylcellulose (NaCMC) and polycarboxylic acids (oxalic, succinic, citric and adipic) as cross-linking agents are synthesized by esterification reaction; one series of NaCMC hydrogels cross-linked with citric acid is prepared with acrylamide and acrylic acid (Aam/Aac) copolymers using the design of semi-interpenetrating polymer networks (semi-IPN), in order to increase their potential application for flocculation purposes. The Infrared spectroscopy (FTIR) of hydrogels confirms the esterification reaction between NaCMC and cross-linking agents. Results of swelling measurements show that citric acid in the amount of 15 wt% gives the hydrogels with the best absorption capacity. The results of Differential scanning calorimetry (DSC) and Thermal gravimetric analysis (TGA) show no significant difference in thermal properties of neat and semi-interpenetrating NaCMC hydrogels. The amorphous nature of hydrogels is confirmed by X-ray diffraction analysis (XRD). The results of flocculation study show that combination of NaCMC network and Aam/Aac copolymer with initial mass ratio of 10/90 creates a theoretical platform for the production of flocculant which could show high efficacy in purifying of water dominated by positively charged particles.     

Poly(HEMA)/cyclodextrin‐based hydrogels for subconjunctival delivery of cyclosporin A

To enhance the solubility and ocular permeability of immunosuppressive agent, cyclosporine A (CsA), three types of delivery systems were prepared using (2‐hydroxypropyl)‐β‐cyclodextrin (HPβCD), and 2‐hydroxyethyl methacrylate (HEMA). Those systems are (i) hydrogels of HPβCD with crosslinking agent ethylene glycol diglycidylether, (ii) poly(HEMA) hydrogels, and (iii) different amounts of HPβCD‐containing poly(HEMA) hydrogels indicated as poly(HEMA‐co‐HPβCD). In the presence of HEMA, hydrogels have desired mechanical integrity with lower equilibrium content than that of hydrogels without HEMA. CsA was loaded into the HPβCD‐based hydrogels by embedding from its aqueous suspensions in higher amounts than that of the poly(HEMA) hydrogels that were loaded by CsA–HPβCD complex solution. Although the poly(HEMA) hydrogels are releasing total CsA in 3 days, long‐term release was realized from HPβCD‐based hydrogels. For subconjunctival administration, regarding to the amounts of loaded CsA, release profiles, and mechanical integrity, the most suitable system is poly(HEMA‐co‐HPβCD) hydrogels in high HPβCD content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40397.     

A novel temperature and pH dual‐responsive hybrid hydrogel with polyhedral oligomeric silsesquioxane as crosslinker: synthesis,characterization and drug release properties

Octavinyl polyhedral oligomeric silsesquioxane (OVPS) is used as the crosslinker instead of N,N′‐methylenebisacrylamide (BIS) to copolymerize with 2‐(dimethylamino)ethyl methacrylate (DMAEMA) or DMAEMA and N‐isopropylacrylamide (NIPAM) to prepare hybrid hydrogels: P(OVPS‐co‐DMAEMA) and P(OVPS‐co‐DMAEMA‐co‐NIPAM). The prepared hydrogels are transparent and show dual response to temperature and pH. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, dynamic mechanical analysis and tensile tests. Their mechanical properties, swelling ratio, deswelling and reswelling behaviors as well as drug release properties were investigated. The results indicate that OVPS can be incorporated into polymer networks in proportion to feed ratios. The P(OVPS‐co‐DMAEMA) hydrogel exhibits more homogeneous interior structure, higher swelling ratio and faster response than the conventional hydrogel prepared with BIS. Moreover, the incorporation of OVPS enhances the compression and tensile properties of the hydrogels. The feed ratios of OVPS and NIPAM have a great effect on volume phase transition temperature, thermal sensitivity, swelling behavior, mechanical properties and drug release properties of the hybrid hydrogels. The prepared dual‐responsive OVPS‐containing hydrogels are expected to be used as biomedical materials in drug release and tissue engineering. © 2014 Society of Chemical Industry     

Controlled release of prednisolone acetate from molecularly imprinted hydrogel contact lenses

The aim of this work was to study the influence of methacrylic acid (MAA) as a comonomer and the application of a molecular imprinting technique on the loading and release properties of weakly crosslinked 2‐hydroxyethyl methacrylate (HEMA) hydrogels, with a view toward their use as reloadable soft contact lenses for the administration of prednisolone acetate (PA). The hydrogels were prepared with HEMA (95.90–98.30 mol %) as a backbone monomer, ethylene glycol dimethacrylate (140 mM) as a crosslinker, and MAA (0, 50, 100, or 200 mM) as a functional monomer. Different PA/MAA molar ratios (0, 1 : 8, 1 : 6, and 1 : 4) in the feed composition of the hydrogels were also applied to study the influence of the molecular imprinting technique on their binding properties. The hydrogels (0.4 mm thick) were synthesized by thermal polymerization at 60°C for 24 h in a polypropylene mold. The hydrogels were then characterized by the determination of their swelling and binding properties in water. Their loading and release properties were also studied in 0.9% NaCl and artificial lachrymal fluid. Increasing the MAA content of the hydrogel and applying the molecular imprinting technique led to an increase in the loading capacity of the hydrogel. The optimized imprinted hydrogel showed the highest affinity for PA and the greatest ability to control the release process, sustaining it for 48 h. The results obtained clearly indicate that the incorporation of MAA as a comonomer increased the PA loading capacity of hydrogel. Our data showed that the molecular imprinting technique also had a significant effect on the loading and release properties of the hydrogels. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Synthesis,characterization, and swelling behavior of new pH‐sensitive hydrogels derived from copolymers of 2‐hydroxyethyl methacrylate and 2‐(diisopropylamino)ethylmethacrylate

The aim of this work was to synthesize and to characterize new pH‐sensitive hydrogels that can be used in the controlled release of drugs, useful for dermal treatments or ophthalmology's therapies. Copolymers containing 2‐hydroxyethyl methacrylate (HEMA) with different amounts of 2‐(diisopropylamino)ethyl methacrylate (DPA) (10 and 30 wt %) and different amounts of crosslinker agent, ethylene glycol dimethacrylate (EGDMA) (1 and 3 wt %) were prepared by bulk photo‐polymerization. The copolymers were fully characterized by using Fourier‐transform infrared (FTIR) spectra, differential scanning calorimetry, thermogravimetric analysis, UV–visible spectroscopy, and measuring water content and dynamic swelling degree. The results show that modifications in the amount of DPA and/or crosslinker in the hydrogel produce variations in the thermal properties. When adding of DPA, we observed an increase in the thermal stability and decomposition temperature, as well as a change in the mechanism of decomposition. Also a decrease in the glass transition temperature was observed with regard to the value for pure pHEMA, by the addition of DPA. The water content of the hydrogels depends on the DPA content and it is inversely proportional to both the pH value and the crosslinking degree. Pure poly‐HEMA films did not show important changes over the pH range studied in this work. The dynamic swelling curves show the overshooting effect associated with the incorporation of DPA, the pH of the solution, and the crosslinking density. On the other hand, no important variations in the optical properties were observed. The synthesized hydrogels are useful as a drug delivery pH‐sensitive matrix. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

智能型聚甲基丙烯酸凝胶的合成与表征

以甲基丙烯酸(MAA)为单体,过硫酸钾(KPS)为引发剂,无机纳米粒子Laponite或者N,N'-亚甲基双丙烯酰胺(BIS)为交联剂,通过原位自由基聚合的方法分别合成了纳米复合聚甲基丙烯酸凝胶和传统型聚甲基丙烯酸凝胶,并利用红外、流变、溶胀性能测试、剥离强度测试等手段对凝胶的性能进行了表征。比较了在不同单体(MAA)含量、体系pH值下,Laponite含量和BIS含量对物理交联法和化学交联法制备的凝胶的交联密度的影响,以及两种凝胶溶胀度随溶液pH值以及温度的变化关系。研究表明:增加单体MAA的含量、增加交联剂Laponite或BIS的含量,以及降低体系的pH值有利于凝胶网状结构的形成。化学交联的传统型聚甲基丙烯酸凝胶具有明显的pH敏感性和温度敏感性,而物理交联的纳米复合聚甲基丙烯酸凝胶具有良好的粘结性能。     

聚甲基丙烯酸/丙烯酰胺pH敏感凝胶的合成与溶胀行为研究

以单体丙烯酰胺(AM)、甲基丙烯酸(MAA),交联剂N-N'亚甲基双丙酰胺(BIS)为原料,通过自由基共聚合成了聚甲基丙烯酸/丙烯酰胺[P(MAA-co-AM)]水凝胶.研究了干凝胶在不同pH溶液中的溶胀动力学,结果表明不同AM、MAA单体配比的凝胶溶胀性具有很大差异,其溶胀率都随着溶液的pH增加而增大,在pH=12和pH=2溶液反复变换时显示可逆溶胀-退溶胀和快速响应特性,溶胀-退溶胀过程中搅拌作用对凝胶响应速率有显著影响.吸水平衡P(MAA-co-AM)水凝胶在酸性及碱性条件下均出现收缩,在pH=2下10 min之内凝胶收缩90%以上,随着pH增大逐渐减慢.通过不同浓度的NaCl与CaCl2溶液研究了溶液离子强度以及反离子的电荷数对凝胶溶胀性影响,在NaCl溶液和水中,呈现反复溶胀-退溶胀响应特性.     

Removal of acidic dye from aqueous solutions using poly(DMAEMA–AMPS–HEMA) terpolymer/MMT nanocomposite hydrogels

In this study, poly(DMAEMA–AMPS–HEMA) terpolymer/montmorillonite nanocomposite hydrogels were prepared by in situ polymerization technique using 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA), 2-acrylamido-2-methlypropane sulfonic acid (AMPS), 2-hydroxyethyl methacrylate (HEMA) monomers in clay suspension media. N,N-methylenebisacrylamide (NMBA) was used as crosslinker and potassium persulfate/potassium bisulfide were used as initiator and accelerator pair. The water absorption capacities and acidic dye (indigo carmine) adsorption properties of the nanocomposite hydrogels were investigated. Adsorption properties of the hydrogels were investigated at different conditions such as different initial dye concentration and contact time. The concentrations of the dyes were determined using UV/Vis Spectrophotometer at wavelength 610 nm. Langmuir and Freundlich isotherm models were used to describe adsorption data and the results clarified that these models were the best-fit for the adsorption of indigo carmine.     

Characterization and In Vitro Drug Release Behavior of (2-hydroxyethyl methacrylate)–co-(2-acrylamido-2-methyl-1-propanesulfonic acid) Crosslinked Hydrogels Prepared by Ionizing Radiation

A series of copolymer hydrogels of 2-hydroxyethyl methacrylate (HEMA)/2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) were prepared by solution free radical polymerization using gamma irradiation. Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy techniques were used to characterize the HEMA/AMPS hydrogels. The swelling behavior of the prepared hydrogels was determined by investigating the time and pH-dependent swelling of the HEMA/AMPS hydrogels of different AMPS content. The drug loading and controlled release behaviors of the hydrogel were evaluated using hydrocortisone acetate as drug model. The results indicated that the release rate of the drug from the hydrogel showed good pH-response.     

Effect of poly(ethylene glycol)-derived crosslinkers on the properties of thermosensitive hydrogels

Three crosslinkers, poly(ethylene glycol) diacrylate (PEGDA), glycerol ethoxylate triacrylate (GETA) and citric acid-(PEG acrylate)₃ (CA-PEGTA) derived from poly(ethylene glycol) (PEG) were synthesized at first. The three series of poly (N-isopropylacrylamide) (PNIPAAm) hydrogels were prepared by photopolymerization with the crosslinkers and compared with a hydrogel based on commercial crosslinker, N,N′-methylene bis-acrylamide (NMBA). The influence of the crosslinker structures and contents on the swelling behaviour, mechanical properties, and drug release of the hydrogels was investigated. The results showed that the hydrogels based on PEGDA and NMBA exhibited the highest and the lowest swelling ratio, respectively. The content of crosslinker of all hydrogel series showed good thermosensitivity and thermo-reversibility. The critical gel transition temperature (CGTT) appeared at 32 °C for the hydrogel based on NMBA, but appeared at about 34 °C for other hydrogels due to higher hydrophilicity of the crosslinker. In the mechanical properties, three-arms crosslinker GETA and CA-PEGTA led to higher mechanical strength than a linear crosslinker PEGDA. A hydrogel based on GETA (NG6) showed the highest shear modulus of 656.9 kPa and Young’s modulus of 1655.0 kPa. The hydrogels containing higher content of crosslinker revealed lower swelling ratio and higher mechanical strength. In the drug release, the hydrogels with higher swelling ratios showed higher drug absorbed. The highest release percentage of caffeine and vitamin B12 for hydrogel based on PEGDA (NP6) could reach 68.3% and 75.4%, respectively. In addition, the bound water and toxicity of the hydrogels were also investigated.

     

Herstellung und charakterisierung von hydrogelen als kontaktlinsenmaterialien

ß-Hydroxyethyl methacrylate = HEMA has been copolymerized with different crosslinkers and swollen in isotonic NaCl solution resulting in hydrogels. Crosslinking is produced more by the length of the crosslinker than by its hydrophilic character. The water content of hydrogels can be increased weakly, if ethylene glycol or glycerin is added to the polymerization mixture. Hydrogels with up to 70percnt; of water have been prepared from HEMA and dimethylaminoethyl methacrylate = DMAEMA and those with up to 90% of water from HEMA and methacrylic acid = MA. Hydrogels from HEMA, DMAEMA and MA, containing up to 70% of water, are distinguished by a neglegible shrinkage during the change from NaCl to CaCl₂ solution as well as by a high oxygen permeation.     

Swelling and mechanical properties of crosslinked hydrogels containing N-vinylpyrrolidone

Copolymers of 2-hydroxyethyl methacrylate/N-vinyl-2-pyrrolidone (HEMA/NVP) and methyl methacrylate (MMA)/NVP were prepared in the presence of varying amounts of ethylene glycol dimethacrylate (EGDMA) and methylene diacrylamide (MDA) as crosslinkers by photopolymerisation. The resultant solid polymers were swollen to equilibrium in water at 293 K to produce hydrogels. These hydrogels were characterised by soluble fraction and equilibrium water content. The gels were also characterised by compression—strain measurements, which enabled the calculation of Young's modulus and effective crosslink density. The differences in these properties of HEMA/NVP and MMA/NVP polymer series and the effects of MDA versus EGDMA as a crosslinker were explained in terms of compositional drift of polymerisation, heterogeneous crosslinking and hydrophilicity/hydrophobicity of the components involved. In comparison with EGDMA, MDA was found to be more effective in reducing the soluble fraction of the polymers studied and to produce less rigid networks when swollen.     

Preparation and Swelling Study of a pH-Dependent Interpolymeric Hydrogel Based on Chitosan for Controlled Drug Release

Novel pH-dependent, biodegradable interpolymeric network (IPN) hydrogels were prepared for controlled drug release investigations. The IPN hydrogels were prepared by irradiation of solutions of N-acryloyglycine (NAGly), polyethylene glycol diacrylate (PEGDA) mixed with chitosan, in the presence of a lower amount of glutaraldehyde as the crosslinker and using 2,2-dimethoxy-2-phenyl acetophenone as the photo-initiator. The equilibrium swelling studies were carried out for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 (simulated gastric and intestinal fluids, respectively). 5-Fluorouracil (5-FU) was entrapped, as a model therapeutic agent, in the hydrogels and equilibrium-swelling studies were carried out for the drug-entrapped gels at 37°C. The in-vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4.     

温度及pH敏感共聚/粘土纳米复合水凝胶的合成与性能研究

以无机粘土为交联剂制备了具有温度、pH双重敏感性的聚（N-异丙基丙烯酰胺-co-甲基丙烯酸-β-羟乙酯）/粘土纳米复合水凝胶（P（NIPA-co-HEMA）/clay）,并用红外和X衍射对其结构和形态进行了表征。在弱碱性（pH=7.4）和25℃条件下,分别研究了温度和不同pH缓冲溶液对该凝胶溶胀度的影响,测定了纳米复合水凝胶的力学性能。结果表明：水凝胶的粘土已被剥离成单片层,且均匀分散在凝胶网络中,起交联作用;P（NIPA-co-HEMA）/clay具有良好的温度、pH双重敏感特性;凝胶的断裂伸长率〉1000%。     

Preparation and drug‐release behavior of minocycline‐loaded poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] films

In this work, biocompatible hydrogel matrices for wound‐dressing materials and controlled drug‐release systems were prepared from poly[hydroxyethyl methacrylate‐co‐poly(ethylene glycol)–methacrylate] [p(HEMA‐co‐PEG–MA] films via UV‐initiated photopolymerization. The characterization of the hydrogels was conducted with swelling experiments, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis (differential scanning calorimetry), and contact‐angle studies. The water absorbency of the hydrogel films significantly changed with the change of the medium pH from 4.0 to 7.4. The thermal stability of the copolymer was lowered by an increase in the ratio of poly(ethylene glycol) (PEG) to methacrylate (MA) in the film structure. Contact‐angle measurements on the surface of the p(HEMA‐co‐PEG–MA) films demonstrated that the copolymer gave rise to a significant hydrophilic surface in comparison with the homopolymer of 2‐hydroxyethyl methacrylate (HEMA). The blood protein adsorption was significantly reduced on the surface of the copolymer hydrogels in comparison with the control homopolymer of HEMA. Model antibiotic (i.e., minocycline) release experiments were performed in physiological buffer saline solutions with a continuous flow release system. The amount of minocycline release was shown to be dependent on the HEMA/PEG–MA ratio. The hydrogels have good antifouling properties and therefore are suitable candidates for wound dressing and other tissue engineering applications. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and Characterization of Porous Poly (N-isopropylacrylamide) /Clay Nanocomposite Hydrogels

Summary  A novel porous PNIPA/Clay nanocomposite hydrogel (NC hydrogel) was prepared by in situ free-radical polymerization using inorganic clay as a crosslinker and calcium carbonate (CaCO₃) particle as a pore-forming agent and subsequent extraction of CaCO₃ with acid. The structure and morphology of the hydrogels were characterized by means of FTIR, TEM and SEM. The temperature responsive behaviors, the deswelling behaviors and the mechanical properties of the NC hydrogels were investigated in detail. The results showed that the swelling ratios below VPTT and the deswelling rates of the NC hydrogels were significantly improved as compared with the hydrogels without introduction of CaCO₃. Moreover, the NC hydrogels thus prepared also exhibited good mechanical properties.     

Asymmetric bihomologous crosslinkers for bicomponent gels—The way to strongly increased elastic moduli

2‐Hydroxyethylmethacrylate (HEMA) and acrylamide (AA) have been copolymerized via free radical mechanism, in the presence of 5 mol % of four different crosslinker systems, the symmetric ethylenglycoldimethacrylate (EGDMA), bisacrylamide (BIS), a mixture of EGDMA and BIS, and the asymmetric acrylamideethylenmethacrylate (METAA). The polymerizations have been monitored with a rheometer, exhibiting the gel obtained with the asymmetric METAA, an elastic modulus that is dramatically increased compared with those of the gels prepared with the other three crosslinker systems. A kinetic analysis using the terminal model has been used to build probabilistic surfaces that give information about how the crosslinker is incorporated into the network. This analysis shows a high dissimilarity between the reactions using the asymmetric and the mixture of symmetric crosslinkers, what has been correlated to the difference in modulus. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Effect of crosslinkers on photocopolymerization of N-vinylpyrrolidone and methacrylates to give hydrogels

N-Vinylpyrrolidone (NVP) and methacrylates are frequently copolymerized to give hydrogels useful as contact lenses. However, the nature of their copolymerization was not well understood. In this study, the effect of a crosslinker on the photocopolymerization of NVP and 2-hydroxyethyl methacrylate (HEMA) was discussed. It was found that crosslinkers with a vinyl carbonate group can copolymerize with NVP better than those containing an allyl group, which, in turn, are better than those containing a methacrylate group. A crosslinker with a vinyl carbonate and a methacrylate group can copolymerize NVP and HEMA the best in terms of giving hydrogels with the highest water content, followed by a crosslinker with a combination of allyl and methacrylate groups. Crosslinkers with only methacrylate or vinyl carbonate groups gave hydrogels either too fragile or too stiff to be useful. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1475–1484, 1997     

Hydrogels based on copolymers of 2‐hydroxyethylmethacrylate and 2‐hydroxyethylacrylate as a delivery system for proteins: Interactions with lysozyme

Hydrogels have attracted considerable attention due to numerous applications, in particular as contact lenses and carriers for sustained drug delivery. The aim of the present work is to characterize the interactions of copolymer hydrogels consisted of 2‐hydroxyethylmethacrylate (HEMA) and 2‐hydroxyethylacrylate (HEA) with a small protein (lysozyme) and to assess the potential applications of these hydrogels as a drug delivery system for sustained release of protein‐based therapeutics. Physicochemical properties of protein‐loaded hydrogels, as well as lysozyme in vitro loading and release and the conformation of the protein released from hydrogels were studied. The effect of copolymer composition on the protein deposition on hydrogels and protein aggregation in the presence of hydrogels was also assessed. The results show that introduction of HEA into the copolymeric hydrogels enhances their suitability as a delivery system for proteins. Copolymerisation of HEMA and HEA allows controlling the physicochemical properties of hydrogels and the protein release rate. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44768.     

Preparation,characterization, and release properties of hydrogels based on hyaluronan for pharmaceutical and biomedical use

Hyaluronic acid (HA) is a natural polysaccharide that is widely distributed in the human body. Its physicochemical properties and high biocompatibility make it a good candidate for biomedical and pharmaceutical uses. In the present work, we report HA‐based hydrogels that could be applied as drug delivery systems or as implants for the treatment of joint diseases. We use butanediol diglycidyl ether as a chemical crosslinker to obtain HA hydrogels. Using a new dissolution tester and ketoprofen (KP) as a model drug, we study the release properties of the hydrogels. We obtain homogeneous and transparent hydrogels with high strength and elasticity. The swelling ratio (SR) depends on the crosslinker concentration and pH of the medium. We also reveal differences between the release profile of KP from swollen and unswollen hydrogels. The characteristics and differences in KP release profiles depending on the SR suggest the possibility of obtaining controlled release from HA‐based hydrogels. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1377‐1382, 2013