Synthesis of full and semi Interpenetrating hydrogel from polyvinyl alcohol and poly (acrylic acid‐co‐hydroxyethylmethacrylate) copolymer: Study of swelling behavior,network parameters,and dye uptake properties

Semi and full interpenetrating network (IPN) hydrogels were synthesized by allowing free radical copolymerization of acrylic acid (AA) and hydroxyethyl methacrylate (HEMA) in the matrix of polyvinyl alcohol (PVOH). Accordingly, four different semi IPN hydrogels were prepared with PVOH: copolymer mass ratio of 1 : 1, 1 : 0.75, 1 : 0.5, and 1 : 0.25. These hydrogels were designated as SEMIIPN1, SEMIIPN2, SEMIIPN3, and SEMIIPN4, respectively. In all of these SEMIIPN, after polymerization PVOH was crosslinked with 2 mass % glutaraldehyde to form the semi IPN structure. In a similar way, sequential full IPN were prepared from PVOH and copolymer of AA and HEMA (designated as PAAHEMA) with same composition except in this case apart from crosslinking of PVOH by 2 mass % glutaraldehyde the PAAHEMA copolymer was further crosslinked with N,N′‐methylenebisacrylamide (NMBA) to produce four full IPN hydrogels designated as FULLIPN1, FULLIPN2, FULLIPN3, and FULLIPN4. All of these semi and full IPN type hydrogels were characterized by carboxylic %, FTIR, UV, DTA‐TGA, XRD, SEM, and mechanical properties. The network parameters, swelling and diffusion characteristics of these hydrogels were also studied. The performance of these semi and full IPNs were compared in terms of their relative abilities for removing varied concentration of rhodamine B (RB) and methyl Violet (MV) dyes from water. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation and characterization of pH-sensitive hydrogel microparticles as a biological on–off switch

The pH-responsive swelling and release behaviors of anionic P(MAA-co-EGMA) hydrogel microparticles having various MAA and EG contents were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. When DC was used as a dispersion stabilizer, well-dispersed hydrogel microparticles having an average diameter of approximately 4 μm were obtained. 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 PMAA. When the MAA content in the hydrogel increased, the swelling ratio increased at a pH above 5 due to the more electrostatic repulsion between the charged groups of MAA. The P(MAA-co-EGMA) hydrogel microparticles showed a pH-responsive release behavior. At low pH (pH 4.0) small amounts of Rh-B were released while at high pH (pH 6.0) relatively large amounts of Rh-B were released from the hydrogels. The difference in the released amount of Rh-B from the hydrogels between pH 4.0 and 6.0 decreased when the MAA content in the hydrogels decreased, which means that the pH-responsive release behavior of the P(MAA-co-EGMA) hydrogel microparticles is closely related to the pH-responsive swelling property of the hydrogel.     

Facile fabrication of poly(vinyl alcohol) gels and derivative aerogels

A facile preparation of poly(vinyl alcohol) (PVOH) hydrogels and their derivative PVOH/montmorillonite clay aerogels is reported, using water as solvent and divinylsulfone as crosslinking agent, making use of an environmentally friendly freeze drying process. The materials exhibit significantly increased mechanical properties after crosslinking. The compressive modulus of an aerogel prepared from an aqueous suspension containing 2 wt% PVOH/8 wt% clay increased 29-fold upon crosslinking, for example. Crosslinking of the polymer/clay aerogels decreased the onset decomposition temperature as measured by thermogravimetric analysis, and generated a more continuous structure at higher clay contents. Such polymer/clay aerogels are promising materials for low flammability applications.     

Interpenetrated Polymeric Networks Based on Gellan and Poly(Vinyl Alcohol)

Abstract

The paper deals with the hydrogels of interpenetrated networks obtained by reticulation of a mixture of gellan and poly(vinyl alcohol) with epichlorohydrine in basic medium and their characterization with respect to the swelling capacity in water. The influence of some factors on the reticulation density (estimated indirectly from the swelling characteristics) is followed, namely: the macromolecular components ratio in the mixture, the polymer/reticulation agent ratio, duration, and temperature. By the proper choice of these parameter values, the hydrogels of preset swelling characteristics can be obtained. Preliminary tests proved the possibility of using these materials as carriers for drugs in view of their controlled release.     

Influence of the nanofiber dimensions on the properties of nanocellulose/poly(vinyl alcohol) aerogels

The investigation of aerogels made from cellulose nanofibers and poly(vinyl alcohol) (PVOH) as a polymeric binder is reported. Aerogels based on different nanocellulose types were studied to investigate the influence of the nanocellulose dimensions and their rigidity on the morphology and mechanical properties of the resulting aerogels. Thus, cellulose nanocrystals (CNCs) with low (10), medium (25), and high (80) aspect ratios, isolated from cotton, banana plants, and tunicates, respectively, microfibrillated cellulose (MFC) and microcrystalline cellulose (MCC) were dispersed in aqueous PVOH solutions and aerogels were prepared by freeze‐drying. In addition to the cellulose type, the PVOH‐ and the CNC‐concentration as well as the freeze‐drying conditions were varied, and the materials were optionally cross‐linked by an annealing step or the use of a chemical cross‐linker. The data reveal that at low PVOH content, rigid, high‐aspect ratio CNCs isolated from tunicates afford aerogels that show the least amount of shrinking upon freeze‐drying and display the best mechanical properties. However, with increasing concentration of PVOH or upon introduction of a chemical cross‐linker the differences between materials made from different nanocellulose types decrease. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41740.     

pH及温度双重敏感性MCM-41/P(AA-co-NIPAAm)的制备和释药性能

通过微波辅助水热法制备了介孔分子筛 MCM-41,并将其与N-异丙基丙烯酰胺(NIPAAm)和丙烯酸(AA)原位聚合生成了一种新型的pH及温度双重敏感型复合材料MCM-41/P(AA-co-NIPAAm),用XRD、N₂吸附-脱附、FT-IR、TGA对所得材料进行表征,结果表明合成了一种新型的复合材料。以氢氯噻嗪为模型药物进行载药性能测试并考察了此释药系统在不同pH及温度环境中的敏感释药行为。结果显示：MCM-41/P(AA-co-NIPAAm)复合材料的载药量达45.8%,并且通过改变环境体系的pH及温度可以有效控制药物的释放。复合材料在肠道靶向给药方面有一定的应用潜力。     

Synthesis of poly(sebacic anhydride): effect of various catalysts on structure and thermal properties

Combining different polymeric systems can be a useful tool to create new networks with different characteristics with respect to the starting materials. In this work, hydrogels composed of gellan gum (GG) and polyethylene glycol dimethacrylate (PEG-DMA) were realized to overcome the fragility problems of physical gels of GG, which limit their biological application as scaffold for tissue engineering. The two polymeric systems were combined using different synthetic approaches, with particular attention to the double network strategy (DN). The influence of several parameters on the mechanical properties, such as the time of diffusion and the molecular weight of PEG-DMA, were evaluated by rheological studies and compressive texture analyses. The hydrogels were also investigated for their ability to swell and release model molecules with different sterical hindrances, such as vitamin B12 and myoglobin. Finally, to estimate the biological safety of the hydrogels, their effect on mitochondrial function of human fibroblasts was investigated.     

Electrostatic immobilization of cetylpyridinium chloride to poly(vinyl alcohol) hydrogels for the simple fabrication of wound dressings with the suppressed release of antibacterial agents

Polymeric systems for antibacterial wound dressings require chemical reactions or syntheses for attaching or incorporating antibacterial moieties into polymer backbones. However, these materials often fail to satisfy the basic requirements, such as easy and inexpensive synthesis. We speculated that a positively charged organic antibacterial agent would be attracted to the polar groups of poly(vinyl alcohol) (PVA) hydrogels and would show suppressed release. PVA hydrogels containing cetylpyridinium chloride (CPC) were prepared by γ irradiation. CPC was barely released from the hydrogels, probably because of electrostatic interactions, and was stable upon γ irradiation. The suppressed release of CPC conferred antibacterial activity against Escherichia coli to the surface of the hydrogels, whereas no inhibition zone was observed around the hydrogels. The CPC‐containing PVA hydrogels were easy to prepare and contained known and safe materials. The simplicity and safety of this procedure for achieving the suppressed release of antibacterial agents were advantages of these CPC‐containing PVA hydrogels. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40456.     

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     

Preparation of poly(acrylic acid)–chitosan hydrogels by gamma irradiation and in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) (AAc) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a gamma irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid content increased. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when the 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30‐kGy radiation dose. Also, an increase of swelling degree with an increase in the pH was noticed and showed 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 the intestinal pH and the rest of the drug had been released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3660–3667, 2003     

Synthesis and Evaluation of AlgNa-g-Poly(QCL-co-HEMA) Hydrogels as Platform for Chondrocyte Proliferation and Controlled Release of Betamethasone

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead^® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.     

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     

pH- and temperature-sensitive semi-interpenetrating network hydrogels composed of poly(acrylamide) and poly(γ-glutamic acid) as amoxicillin controlled-release system

Hydrogels of semi-interpenetrating networks composed of poly(acrylamide) (PAAm) and poly(γ-glutamic acid) (γ-PGA) with different proportions were studied as potential amoxicillin controlled-release devices. The effects of the hydrogels composition, pH, and temperature on the kinetics and final release of amoxicillin were determined in batch experiments. The release kinetic tests were conducted using a buffer solution as the release medium under pH conditions of 3 and 7.2, and temperature of 25, 37, and 45 °C. The final percentage of amoxicillin released from the hydrogels was found to increase with temperature, pH, and the amount of γ-PGA in the hydrogels formulation. Overall, equilibrium conditions in the kinetics experiments were achieved within 240 min of hydrogel–solution contact. The overall rate of amoxicillin release was represented with a two-parameter empirical model as a function of time.     

Investigation of ZnO‐release behavior of poly(N‐isopropylacrylamide‐co‐maleic acid)/ZnO composite hydrogels by differential pulse polarography

Poly(N‐isopropylacrylamide‐co‐maleic acid)‐zinc oxide [P(NIPA/MA)/ZnO] composite hydrogels, containing a definite amount of ZnO, were prepared from N‐isopropylacrylamide (NIPA) and maleic acid (MA) monomers with 0–31.15 mol % MA in aqueous saturated zinc oxide solutions by radiation‐induced polymerization and gelation using γ rays from a ⁶⁰Co source. The amounts of released ZnO from these composite hydrogels were determined by differential pulse polarography (DPP) using the characteristic peaks obtained at about –1,000, ?1,050, and –1,300 mV at pH 2.0, 5.5, and 7.05, respectively. It was found that the ZnO‐release behavior of P(NIPA/MA)/ZnO composite hydrogels depended strongly on the MA content and pH of the medium.     

Development of dual‐triggered in situ gelling scaffolds for tissue engineering

Hydrogel‐forming materials that mimic the three‐dimensional architecture and properties of tissue are known to have a positive effect on cellular differentiation and growth. A subset of those are in situ gels, which utilise in vivo conditions like pH (e.g. acetate phthalate), temperature (e.g. poloxamer) and ionic concentration (e.g. Gelrite?), and can be used to facilitate the delivery of cells to an affected tissue. Hence, we have developed in situ hydrogels based on gellan and hydroxypropylmethylcellulose (HPMC), which are known to be triggered through ions and temperature, respectively, as matrices to deliver cells. Gellan/HPMC blends had a lower gelation temperature than gellan alone crosslinked with calcium, suggesting the role of the dual trigger. Average storage modulus at a frequency of 10 Hz for gellan crosslinked with 3 mmol L^?1 calcium was 4.53 × 10³ Pa; for 9:1 gellan/HPMC crosslinked with 3 mmol L^?1 calcium was 5.59 × 10³ Pa; and for 8:2 gellan/HPMC crosslinked with 3 mmol L^?1 calcium was 2.13 × 10³ Pa, suggesting tunable stiffness by changing the gellan‐to‐HPMC ratio. Hydrophilicity was confirmed using goniometry with a contact angle much less than 90°, facilitating the passage of cells and electrolytes when using the gels as scaffolds. The gels were also found to be porous and non‐toxic to fibroblast cell line L929 and osteosarcoma cell line MG‐63, which, when encapsulated within the gels, were able to grow and proliferate. These blended hydrogels are suitable as scaffolds to encapsulate cells, with tunable stiffness modulated by varying the concentration of gellan and HPMC. © 2014 Society of Chemical Industry     

Design and fabrication of a triple-responsive chitosan-based hydrogel with excellent mechanical properties for controlled drug delivery

A pH-, temperature- and salinity responsive hydrogel with enhanced mechanical performance was developed based on semi interpenetrating network that was formed as a result of concurrent free radical polymerization of acrylic acid (AA), oligo(ethylene glycol) methacrylate (OEGMA) and 2-(2-methoxyethoxy) ethyl methacrylate (MEO₂MA) along with chitosan (CS) for controlled drug delivery. The mechanical behaviors and swelling properties of these hydrogels were systematically investigated, and the results indicated that they were strongly affected by the content of AA and MEO₂MA and exhibited strong pH-, temperature and salinity sensitivity. Bovine serum albumin (BSA) and 5-Fluorouracil (5-Fu) were used as the model drugs to evaluate the sustained release of the hydrogel. The result indicated that the amount of both drugs released was relatively low in acidic condition (pH 1.2) but high in neutral environment (pH 7.4), and the release rate of the drugs was slower at 37 °C than that at 25 °C. Cytotoxicity results suggested that the blank hydrogels had negligible toxicity to normal cells, whereas the 5-Fu-loaded hydrogels remained high in cytotoxicity for LO2 and HepG2 cancer cells. These results suggest that the synthesized hydrogels have the potential to be used as an effective pH/temperature sustainable site-specific oral drug delivery in intestine and colon.     

Drug release behavior of electrical responsive poly(vinyl alcohol)/poly(acrylic acid) IPN hydrogels under an electric stimulus

The electrically modulated properties of interpenetrating polymer networks (IPN) composed of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAAc) under electric field were investigated for drug delivery systems. PVA/PAAc IPNs with various compositions were synthesized by a sequential method, that is, ultraviolet polymerization of AAc in the mixture of PVA and aqueous AAc monomer solution, followed by a freeze‐thawing process to prepare elastic hydrogels. The amount of loaded drug significantly increased with the content of PAAc containing ionizable groups in IPN. The amount of introduced ionic drug (cefazoline) was greater than that of the nonionic drug (theophylline). Release behaviors of drug molecules from negatively charged PVA/PAAc IPN were switched on and off in a pulsatile pattern depending on the applied electric stimulus. The released amount and the release rate of drug were influenced significantly by the applied voltage, ionic group contents in IPN, ionic properties of drug solute, and the ionic strength of release medium. In addition, the ionic properties of drug molecules dramatically affected release behaviors, thus the release of ionic drug was much more enhanced than that of the nonionic drug. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 1752–1761, 1999     

Controlled release of diltiazem hydrochloride

A new type of complex reservoir–matrix system for the controlled delivery of diltiazen hydrochloride was developed. This capsule-type device was designed for oral administration to humans and/or animals. It contained (i) an appropriate amount of the drug in a compartment; (ii) a swelling-controlled membrane which was prepared by mixing polymeric materials with another appropriate amount of the drug; and (iii) a water-soluble gelatin capsule as container. The swelling-controlled membranes were prepared from poly(2-hydroxyethyl methacrylate) hydrogels. The effect of pH on the swelling of the hydrogels was studied. In-vitro dissolution testing was carried out to evaluate the release of the drug using a continuous-flow method. Zero-order release kinetics was obtained over a period of 12 h.     

Sustained Release of Metoprolol Tartarate from Radiation-Grafted pH-Responsive Hydrogels

pH-responsive hydrogels composed of methacrylic acid (MAA) grafted on poly(ethylene oxide)-poly(vinylpyrrolidone)(PEO-PVP) network were made by electron beam irradiation technique. The grafting was carried out at various concentrations of MAA with different irradiation doses. The gels were characterized by IR, DSC and SEM techniques. The swelling behavior of the gels was studied under different pH conditions. The swelling parameters were evaluated. The mode of water diffusion into the gels was found to be structure-dependent. The pH responsiveness of the gels was evident from the enhanced swelling of the gels with increasing pH of the medium. The suitability of these gels as matrix materials for stimuli-responsive sustained-release drug formulations was studied. The in vitro release profile of an antihypertensive drug, metoprolol tartarate, from these gels was studied at pH 1.2 and 7.4. The extent of drug release is found to be pH-dependent. The data were analyzed to understand the mechanism of drug release from the gels. The gels exhibited diffusion-controlled release behavior. Drug release kinetic analysis indicated “first order” release where the amount of drug released is dependent on the matrix drug load and the value of the diffusion coefficient indicated anomalous diffusion.     

Thermoreversible hydrogels. XV. Swelling behaviors and drug release for thermoreversible hydrogels containing silane monomers

Three series of thermosensitive copolymeric hydrogels were prepared from [3‐(methacryloyloxy)propyl]trimethoxysilane (MPTMOS), [2‐(methacryloyloxy)ethoxy]trimethylsilane (METMS), and (methacryloyloxy)trimethylsilane (MTMS), referred to as the silane monomer, and N‐isopropylacrylamide (NIPAAm) by solution polymerization. The influence of the structures and amounts of silane monomers on the swelling and drug‐released behaviors were studied. The results showed that, because of the hydrophobicity of the silyl group, the more silane monomers in the copolymeric hydrogels the lower was the swelling ratio of the gels. The hydrophobicity of the silyl group affected the swelling mechanism, which resulted from the non‐Fickian diffusion for the gels. The copolymeric gels clearly exhibited gel transition temperatures. The copolymeric hydrogels could be applied to a drug‐release and drug‐delivery system. The delivery amount would approach a steady state after three cycle operations of delivery. The gels also showed an on–off switch behavior on drug release depending on the temperature, and the gels released more CV with the gels in a swollen state. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2523–2532, 2002