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.

     

Synthesis and Characterization of Injectable Photocrosslinking Poly (ethylene glycol) Diacrylate based Hydrogels

The poly (ethylene glycol) diacrylate (PEGDA)-based hydrogels were prepared by UV radiation under nitrogen, using PEGDA and 2-hydroxyethyl methacrylate (HEMA) as precursors. The PEGDA and HEMA precursors were respectively added into distilled water at a predetermined feed ratio. 2-Hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure2959) was used as a photoinitiator. The PEGDA-based hydrogels were characterized by FT-IR spectra, interior morphology, equilibrium swelling ratio, and Dynamic contact angle (DCA). The results showed: (1) -C=C- bonds of PEGDA and HEMA disappeared after photocrosslinking, which indicated hydrogel formation by consuming -C=C- bonds; (2) swelling ratio of the hydrogels were greatly influenced by the additive precursor ratios and microporous net; (3) with HEMA content increasing in PEGDA-based hydrogels, equilibrium water content (EWC) increased and the contact angle decreased, which resulted from the strong H-bonding interactions of HEMA between the polymer and water.     

温度和pH双重敏感性P(DEA-co-DMAEMA)/Na2WO4水凝胶的合成与表征

以N,N-二乙基丙烯酰胺(DEA)和甲基丙烯酸二甲氨基乙酯(DMAEMA)为单体,N,N-亚甲基双丙烯酰胺(BIS)为交联剂,采用一锅法制备了温度和p H双重响应性P(DEA-co-DMAEMA)/Na_2WO_4水凝胶。考察了Na_2WO_4的引入对水凝胶的结构、温度和p H响应性能的影响。结果表明:复合水凝胶中除了化学交联外,还存在Na_2WO_4与聚合物间由于氢键和配位作用产生的物理交联;复合水凝胶的低临界相转变温度(LCST)随着Na_2WO_4质量分数的增加呈线性降低,当Na_2WO_4质量分数从0增至3%时,LCST由41.6℃降至34.4℃;复合水凝胶表现出双重p H响应性,即在酸性条件下溶胀,中性条件下溶胀率减小,碱性条件下溶胀率又升高。     

聚丙烯酸水凝胶的制备及其对结晶紫的控制释放

通过自由基聚合制备出聚丙烯酸水凝胶,考察了交联剂、单体中和度、盐对水凝胶溶胀性能的影响,以结晶紫为模板研究了水凝胶对结晶紫的控制释放性能。结果表明,交联剂用量在0.8%,单体中和度为70%时水凝胶溶胀性能最佳;在相同条件下,聚丙烯酸水凝胶的溶胀率随盐溶液浓度的增大而降低;聚丙烯酸水凝胶对药物具有良好的控制释放性能,对结晶紫的释放为扩散机制。     

Controllable properties and microstructure of hydrogels based on crosslinked poly(ethylene glycol) diacrylates with different molecular weights

This work describes a comprehensive study of hydrogels based on polyethylene glycol diacrylates (PEGDAs) with the molecular weight (MW) range of 400–2000. The blends of low‐ and high‐molecular weight PEGDA macromers with different ratios were photopolymerized under visible light irradiation, using a blue light sensitive photoinitiator Irgacure819, at the total polymer concentration of 60 wt %. Swelling ratios, wetting property, elastic moduli, transparency, and the microstructure of the resulting hydrogels were investigated. Among them, equilibrium water contents, hydrophilicity, and mesh size of the hydrogels increased while the elastic moduli decreased when increased the PEGDA MW or the content of higher MW PEGDA in the blends. Most of the hydrogels possessed excellent transparency in visible region. The viability of L929 cells on the surface of hydrogel was also estimated. All the selected hydrogels exhibited a relatively high proliferation rate, which demonstrated this hydrogel system with photoinitiator Irgacure819 had good biocompatibility. These results show the properties of PEGDA hydrogel could be easily adjusted by varying PEGDA MW or the ratios of low‐ and high‐MW macromers in the composites. It could be helpful for the design of proper PEGDA hydrogels in the applications as tissue engineering or drug delivery system. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

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

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

Novel metronidazole-loaded hydrogel as a gastroretentive drug delivery system

A metronidazole-loaded hydrogel was synthesized by free radical polymerization using dimethylaminoethyl methacrylate (DMAEMA) monomer and triethyleneglycol dimethacrylate (TEGDA) and methylene bisacrylamide (MBA) as cross-linkers. The DMAEMA hydrogels were cross-linked with 5 and 10% MBA or with 0.1, 0.5, 1 and 4% TEGDA as cross-linking agents. Ammonium persulfate and tetramethyl ethylene diamine were used as initiator and catalyst, respectively. The prepared hydrogels were characterized, and the effect of cross-linking agent content on the swelling behavior and in vitro drug release of hydrogels was investigated. The results of X-ray diffractometry, differential scanning calorimetry and Fourier transform infrared spectroscopy studies indicated that the prepared hydrogels possessed an amorphous morphology and there was not any interaction between the hydrogel polymers and metronidazole as drug, which resulted in the dependence of drug release on the physicochemical characteristics of hydrogel such as swelling, polymer erosion, and surface morphology. According to the results, the hydrogel containing 0.5% TEGDA which was prepared by freeze-drying method exhibited a porous structure with a high swelling ratio and displayed a sustained and complete drug release. It could be concluded that the hydrogel developed by this facile method is a good candidate with a potential for use in gastroretentive drug delivery systems.     

PVA/Fe2O3磁敏感性水凝胶的制备及性能

采用循环冷冻-解冻方法制备了聚乙烯醇(PVA)/Fe2O3磁敏感性水凝胶. 考察了水凝胶的力学性能、溶胀性能和磁敏感性,并用扫描电镜观察了其表面形貌. 结果表明,当Fe2O3含量为1%(w)时,水凝胶的力学性能最好;水凝胶的溶胀度和脱水率随时间增加有相似的变化趋势,都随磁性粒子含量升高而降低;溶胀性能降低其交联程度增加;PVA和Fe2O3相容性较好;水凝胶在3000 Oe的磁场强度下达到饱和,呈现出很强的顺磁性,磁滞损耗较多,表明具有较好的磁敏感性.     

Influence of Process Variables on the Physical Properties of Gelatin/SA/HYA Composite Hydrogels

A novel composite hydrogel based on gelatin, sodium alginate (SA) and hyaluronic acid (HYA) was fabricated by freeze-drying method using 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide (EDC) as a cross-linker. The effects of chemical cross-linking, including cross-linker content and cross-linking time, on the morphology, swelling ratio and compressive strength of the gelatin/SA/HYA hydrogel were investigated. The influence of pH value of the swelling medium on the swelling ratio of the gelatin/SA/HYA composite hydrogel was also studied. The results showed that the gelatin/SA/HYA composite hydrogel had a three-dimensional interconnected structure and the pore size decreased with increasing EDC concentration. The IR absorption peak intensity of the gelatin/SA/HYA hydrogel has no obvious variety with increasing EDC content. The swelling ratio of the gelatin/SA/HYA hydrogel decreased with increasing cross-linker content and cross-linking time; however, the compressive strength increased with increasing EDC content and cross-linking time. The hydrogel swelling peak reached at pH 7. Therefore, the architecture and the physical properties of the gelatin/SA/HYA composite hydrogel can be adjusted by controlling the chemical cross-linking conditions and pH value of swelling medium.     

UV-curing of simultaneous interpenetrating network silicone hydrogels with hydrophilic surface

Simultaneous interpenetrating polymer network silicone hydrogels have been prepared by UV-initiated free radical/cationic hybrid photopolymerization of a mixture of methacrylate macromonomer polyethylene glycol diacrylate (PEGDA) and vinyl ether terminated polydimethylsiloxane macromonomer (VESi). The consumption of each macromonomer upon UV-irradiation was monitored in situ by real-time infrared spectroscopy. The analysis of transmission electron microscope indicated that the silicone hydrogels exhibited a heterogeneous morphology. The physicochemical properties of the silicone hydrogels, such as water content, ion permeability, oxygen permeability, and contact angle were investigated. The results showed that water content and ion permeability increased with the PEGDA content in the formulation, and the silicone hydrogels exhibited excellent oxygen permeability with the highest D _k of 248?barrer. The results of contact angle measurements indicated that the silicone hydrogels possessed hydrophilic surfaces with the lowest water contact angle of 32°. The study of the protein resistance revealed that the amount of protein adsorbed was significantly reduced with the PEGDA content in the formulation.     

Enhanced adsorption properties of interpenetrating polymer network hydrogels for heavy metal ion removal

In this study, sequential interpenetrating polymer network (IPN) hydrogels based on poly(polyethylene glycol diacrylate) poly(PEGDA) and poly(methacrylic acid) (PMAA) were prepared with enhanced adsorption properties for heavy metal ion removal. The swelling behavior and mechanical property of the IPN hydrogels were characterized. It was found that swelling ratio increased, and mechanical strength decreased with the PMAA content in the IPN. The IPN hydrogels were used to remove heavy metal ions from aqueous solution under the non-competitive condition. The effects of pH values of the feed solution at the range of 3–5 and PMAA content in the IPN on the adsorption capacity were investigated. The results indicated that the adsorption capacity of the IPN hydrogels increased with the pH values and PMAA content in the IPN. Furthermore, the synergistic complexation of metal ions with two polymer networks in the IPN was found in the adsorption studies. Regeneration studies suggested that metal rebinding capacity of the IPN hydrogels did not change significantly through repeated applications compared with the first run. It was concluded that the poly(PEGDA)/PMAA hydrogels could be used as fast-responsive, high capacity, and renewable sorbent materials in heavy metal removing processes.     

Photo‐crosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels from low molecular weight prepolymer: Swelling and permeation studies

The aim of this work was to assess the diffusive properties of poly(ethylene glycol) diacrylate (PEGDA)‐based hydrogels, derived from low MW prepolymers, in view of potential biomedical applications. Several hydrogels were synthesized through UV irradiation of PEGDA solutions for different exposure times. Swelling measurements in distilled water were performed to estimate the yielded crosslink density, while swelling tests at 37 °C in selected media allowed to analyze the mesh size changes induced by various pH and ionic strength (IonS) conditions. The transport of glucose and insulin through thin hydrogel membranes was finally assessed in a modified Ussing chamber at physiological values of pH and IonS (7.4 and 150 mM, respectively). Results showed that the swelling was dependent on the IonS (with swelling reductions up to 20–30% for IonS increases in the range 0–300 mM) and, to a lesser extent, on the pH of the surrounding medium (with swelling increments of about 10% for increasing pH in the range 2.5–11). All hydrogels were also permeable to glucose and insulin, which displayed comparable diffusion coefficients (in the order of 10^?6 cm²/s). Specific interactions between glucose and the polymer chains were evidenced by values of the partition coefficient higher than unity. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44380.     

Quantitative analysis of the cross-linked structure of microgels using fluorescent probes

Properties of polymeric microgels are influenced by the internal polymer cross-linked structure, but tools to quantitatively analyze this internal structure are limited. With the finding that polymer networks alter the diffusivity and subsequent excimer formation of pyrene, this study used the ratio between pyrene excimer and monomer emission to determine the number of cross-links (N) and average pore size (ξ) in poly(ethylene glycol) diacrylate (PEGDA) microgels. A calibration curve to relate pyrene emission to N and ξ in PEGDA hydrogels was prepared and used to calculate N and ξ in PEGDA microgels. The pyrene emission indicated that PEGDA microgels had a higher cross-linking density and a smaller average pore size when compared with bulk cross-linked hydrogels of the same PEGDA concentration. The analytical method demonstrated in this study may be useful for fine-tuning polymeric microgel properties for a broad array of applications.     

Improved mechanical and swelling behavior of the composite hydrogels prepared by ionic monomer and acid-activated Laponite

A composite hydrogel (CH) with much improved mechanical and swelling properties was prepared using an ionic monomer and acid-activated Laponite XLS which was used as a cross-linking agent. Addition of acid-activated clay solved the gelation problem when ionic monomers were added to clay mineral dispersions. Reaction of Laponite XLS with sulfuric acid yielded amorphous silica. A dispersion of the acid-activated Laponite and the monomers was used to synthesize composite hydrogels by in-situ polymerization. The FT-IR spectra and rheological results of the composite hydrogels demonstrated the formation of a network. The equilibrium swelling ratios of composite hydrogels (> 6000 g/g) were more than 18 times larger than traditional organic cross-linked hydrogels. The moduli G′ and G″ in the observed frequency range were about 4 and 10 times larger than those of organic cross-linked hydrogel (OR gel). The improvement in both the equilibrium swelling ratio and mechanical strength was attributed to the homogeneous cross-linked network structure.     

温度和pH双重刺激响应型水凝胶的溶胀性能研究

以丙烯酰胺、丙烯酸和双丙酮丙烯酰胺为原料,以N,N'-亚甲基双丙烯酰胺为交联剂,2-酮戊二酸为引发剂,采用光引发聚合方法制备出系列新型温度和pH响应型水凝胶。考察了交联剂用量、水凝胶组成、温度和pH值对凝胶溶胀性能的影响。结果表明,随交联剂用量的增加,凝胶的溶胀率减小,随凝胶组成中AA含量的增加,凝胶的溶胀率增加。凝胶的溶胀率随温度的升高而减小,随pH值的增大而增加,表现出显著的温敏和pH敏感性。     

Preparation of a novel pH-sensitive hydrogel based on acrylic acid and polyhedral oligomeric silsesquioxane for controlled drug release of theophylline

Hydrogels based on pH-sensitive polymers are of great interest as potential biomaterials for the controlled delivery of drug molecules. In this study, a novel pH-sensitive copolymer hydrogel based on acrylic acid (AA) monomer by free-radical solution polymerization were synthesized with organic–inorganic cross-linking agent of octavinyl polyhedral oligomeric silsesquioxane (OVPOSS). And its properties were compared with conventional hydrogels using N,N′-methylenebisacrylamide (MBA) as cross-linking agent. The copolymers were characterized by Fourier transform infrared spectra and differential scanning calorimetry. The morphology after swelling was presented by scanning electron microscopy. Swelling behaviors in different pH and potential applications in controlled drug delivery of the hydrogels were also examined. The results showed that both hydrogels were pH sensitive. However, as the addition of OVPOSS limited the movement of the molecular chain segment, the swelling ratio and the drug-release rate of theophylline in SGF decreased obviously when using OVPOSS as cross-linking agent, comparing with P(MBA-co-AA) hydrogels. The results in this study suggested that P(OVPOSS-co-AA) could serve as potential candidate for theophylline drug delivery.     

N-vinylpyrrolidone/acrylic acid/2-acrylamido-2-methylpropane sulfonic acid based hydrogels: Synthesis,characterization and their application in the removal of heavy metals

In this work, the synthesis of N-vinylpyrrolidone/acrylic acid/2-acrylamido-2-methylpropane sulfonic acid (NVP/AAc/AMPS) based hydrogels by UV-curing technique was studied and their swelling behavior, heavy metal ion recovery capabilities were investigated. The structures of hydrogels were characterized by FT-IR analysis and the results were consistent with the expected structures. Thermal gravimetric analysis of hydrogels showed that the thermal stability of hydrogel decreases slightly with incorporation of AMPS units into the structure. In addition, the morphology of the dry hydrogel sample was examined by SEM. According to swelling experiments, hydrogels with higher AMPS content gave relatively higher swelling ratio compared to neat hydrogel. These hydrogels were used for the separation of Cd(II), Cu(II) and Fe(III) ions from their aqueous solutions. The influence of the uptake conditions such as pH, time and initial feed concentration on the metal ion binding capacity of hydrogel was also tested. The selectivity of the hydrogel towards the different metal ions tested was Cd(II) > Cu(II) > Fe(III). It was observed that the specific interaction between metal ions and ionic co-monomers in the hydrogel affected the metal binding capacity of the hydrogel. The recovery of metal ions was also investigated in acid media.     

Preliminary swelling and dye sorption studies of acrylamide/4-styrenesulfonic acid sodium salt copolymers and semi-interpenetrating polymer networks composed of gelatin and/or PEG

Semi-IPN hydrogels based gelatin (GEL) and/or poly (ethylene glycol) (PEG) were prepared with acrylamide (AAm) and 4-styrenesulfonic acid sodium salt, (SSS) as a water adsorbent for cationic dye (methyl violet, MV) sorption. For this, chemically crosslinked copolymer of AAm/SSS copolymer with GEL and/or PEG were prepared by polymerization of aqueous solution of AAm and SSS using ammonium persulfate (APS)/N,N,N′,N′-tetramethylethylenediamine (TEMED) as redox initiating pair in presence of poly(ethylene glycol)diacrylate (PEGDA) as crosslinker. FT-IR analysis was used to identify the presence of different repeating units in the semi-IPNs. Surface morphology was characterized by scanning electron microscopy (SEM). Some swelling and diffusion characteristics were calculated for different semi-IPNs and hydrogels prepared under various formulations. Water uptake, and dye sorption properties of the crosslinked polymeric systems such as AAm/SSS, AAm/GEL/SSS, AAm/PEG/SSS and AAm/GEL/PEG/SSS hydrogel systems were investigated as a function of chemical composition of the hydrogels. MV have used in sorption studies.     

High strength and bioactivity polyvinyl alcohol/collagen composite hydrogel with tannic acid as cross-linker

Hydrogels have great potential applications in biomedical materials, but their applications in complex physiological environments are severely limited by their weak strength and biotoxicity. Generally, synthetic polymer hydrogels and natural polymer hydrogels have complementary advantages in terms of mechanical strength and biological activity. Herein, tannic acid (TA), a natural material, was introduced into the polyvinyl alcohol/collagen (PVA-COL) double network to prepare a hydrogel (PVA-COL-TA) with good bioactivity and mechanical properties. The tensile strength of the composite hydrogel can reach up to 20 times that of the pure PVA hydrogel. And the hydrogel after swelling under physiological conditions also exhibits stable mechanical properties. The introduction of TA can reduce the degradation rate of COL, enabling it to continue to exert biological activity. in vitro cytocompatibility experiments showed that PVA-COL-TA hydrogel has good sustained biological activity and the potential for biomedical materials.     

A novel pH‐sensitive and freeze‐thawed carboxymethyl chitosan/poly(vinyl alcohol) blended hydrogel for protein delivery

BACKGROUND: Blended hydrogels are widely applied in medical fields. They can provide many advantages, such as biocompatibility and biodegradability. Many materials and methods are used to obtain blended hydrogels. In this work, carboxymethyl chitosan (CMCS) and poly(vinyl alcohol) (PVA) blended hydrogels were prepared using the freezing and thawing technique. The properties of the hydrogels prepared, i.e. gel fraction, swelling and pH‐responsive behaviors, were investigated. RESULTS: The gel fraction increased with increasing time of freezing and thawing as determined through gravimetric analysis. It was also found that the equilibrium degree of swelling improved obviously due to the addition of CMCS compared to pure PVA hydrogel. The blended hydrogel with composition CMCS/PVA 80/20 (by weight) possessed the highest swelling ratio. The results of the influence of pH values on the swelling behavior showed that minimum swelling ratios of the hydrogels occurred near the isoelectric point of CMCS. Protein release studies were performed under various pH conditions: the release was much slower under acid than under basic conditions. The release showed a burst in the first 15 h and then steadily increased. CONCLUSION: The addition of CMCS can improve the physical properties of pure PVA hydrogels and provide pH sensitivity. It is concluded that PVA hydrogels containing CMCS could be potentially applied as oral delivery systems for protein drugs. Copyright © 2009 Society of Chemical Industry