Insulin release behavior of poly(N-isopropylacrylamide-co-N-vinyl-2-pyrrolidone) hydrogel based on modified melamine crosslinkers

Novel hydrogels based on poly(N-isopropylacrylamide-co-N-vinyl-2-pyrrolidone) (PNIPAAm/PNVP), were synthesized by solution radical polymerization using water as solvent and different weight percentage of crosslinkers ranging from 0.5 to 4%. The monomer mol ratios of NIPAAm/VP (0.9/0.1, 0.5/0.5, and 0.1/0.9) were used in all cases. N,N′-methylenebisacrylamide (MBA) and the new synthesized N,N,N-triacrylamido melamine (MAAm) were used as crosslinkers. The swelling parameters such as the swelling ratio Q, equilibrium water content (EWC), volume fraction of polymer φ_p and volume fraction at crosslinking φ_r were calculated from swelling measurements at different temperatures. The lower critical solution temperatures (LCST) of the prepared hydrogels were measured using DSC technique. The data of LCST indicated that the NIPAAm/VP crosslinked with MAAm or MBA showed reversible swelling and shrinking with temperature changes. The temperature dependence of swelling ratio and response kinetics upon heating or cooling was also investigated to understand the smart properties, i.e., temperature sensitive properties of these smart hydrogels. The in vitro release experiments were carried out at 22 and 37°C, respectively, to investigate the effect of temperature-sensitive property of these PNIPAAm/PNVP hydrogels crosslinked with MAAm and MBA crosslinkers on insulin release profiles.     

A simple FTIR spectroscopic method for the determination of the lower critical solution temperature of N‐isopropylacrylamide copolymers and related hydrogels

Linear and crosslinked polymers based on N‐isopropylacrylamide (NIPAAm) exhibit unusual thermal properties. Aqueous solutions of poly(N‐isopropylacrylamide) (PNIPAAm) phase‐separate upon heating above a lower critical solution temperature (LCST), whereas related hydrogels undergo a swelling–shrinking transition at an LCST. A linear copolymer made of NIPAAm/acryloxysuccinimide (98/2 mol/mol) and two hydrogels with different hydrophilicities were prepared. Fourier transform infrared (FTIR) spectroscopy was employed to determine the transition temperature and provide insights into the molecular details of the transition via probing of characteristic bands as a function of temperature. The FTIR spectroscopy method described here allowed the determination of the transition temperature for both the linear and crosslinked polymers. The transition temperatures for PNIPAAm and the gel resulting from the crosslinking with polylysine or N,N′‐methylenebisacrylamide (MBA) were in the same range, 30–35 °C. For the gels, the transition temperature increased with the hydrophilicity of the polymer matrix. The spectral changes observed at the LCST were similar for the free chains and the hydrogels, implying a similar molecular reorganization during the transition. The C H stretching region suggests that the N‐isopropyl groups and the backbone both underwent conformational changes and became more ordered upon heating above the LCST. An analysis of the amide I band suggests that the amide groups of the linear polymer were mainly involved in hydrogen bonding with water molecules below the LCST, the chain being flexible and disordered in a water solution. During the transition, around 20% of these intermolecular hydrogen bonds between the polymer and water were broken and replaced by intramolecular hydrogen bonds. Similar changes were also observed at the LCST of a gel crosslinked with MBA. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 907–915, 2000     

Poly(methacrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) hydrogels: Investigation of pH‐ and temperature‐dependent swelling characteristics and their characterization

Novel poly(methacrylamide‐co‐2‐acrylamido‐2‐methyl‐ 1‐propanesulfonic acid) (poly(MAAm‐co‐AMPS)) hydrogels were synthesized by free radical polymerization of methacrylamide (MAAm) and 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid (AMPS) in deionized water at 60 °C by using ammonium peroxydisulfate (APS), N,N′‐methylenebisacrylamide (MBAAm) and N,N,N′,N′‐tetramethylethylenediamine (TEMED) as initiator, crosslinker, and activator, respectively. To investigate the effects of feed content on the pH‐ and temperature‐dependent swelling behavior of poly(MAAm‐co‐AMPS), molar ratio of MAAm to AMPS in feed was varied from 90/10 to 10/90. Structural characterization of gels was performed by Fourier transform infrared (FTIR) spectroscopy using attenuated total reflectance (ATR) technique. Thermal and morphological characterizations of gels were performed by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Although an apparent pH‐sensitivity was not observed for the poly(MAAm‐co‐AMPS) gels during the swelling in different buffer solutions, their temperature‐sensitivity became more evident with the increase in AMPS content of copolymer. Thermal stability of poly(MAAm‐co‐AMPS) gels increased with MAAm content. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010     

Synthesis and Characterization of Hydrogels Based on Gamma Radiation Copolymerization of N‐isopropylacrylamide and Ethylene Glycol Dimethacrylate Monomers

Hydrogels based essentially on N‐isopropylacrylamide (NIPAAm) and different ratios of ethylene glycol dimethacrylate (EGDMA) monomer were synthesized by gamma radiation copolymerization. The thermal decomposition behavior of NIPAAm/EGDMA hydrogels was determined by thermogravimetric analysis (TGA). The effect of temperature and pH on the swelling behavior was also studied. The results showed that the ratio of EGDMA in the comonomer feeding solution has a great effect on the yield product, gel fraction and water content in the final hydrogel. In this regard, it was observed that the increase of EGDMA ratio decreased these properties. The TGA study showed that all the compositions of NIPAAm/EGDMA hydrogels displayed higher thermal stability than the hydrogel based on pure PNIPAAm hydrogel. The swelling kinetics in water showed that pure PNIPAAm and NIPAAm/EGDMA hydrogels reached equilibrium after 6 h. However, NIPAAm/EGDMA hydrogels show swelling in water lower than pure PNIPAAm. The results showed that the swelling character of pure PNIPAAm and NIPAAm/EGDMA hydrogels was affected by the change in temperature within the temperature range 25–40°C, and showed a reversible change in swelling in the pH range 4–7 depending on composition.     

The use of hydrophobic spacers in the development of new temperature- and pH-sensitive polymers

The preparation and characterization of two series of methacrylic acid derivative polymers is described. One series contains aliphatic spacers with one to ten methylene units, while the other series includes an aromatic ring with changes in the position of the acid, as spacer. Both series of polymers were obtained as methoxy-ester protected acid polymers and as polymers containing free acid groups in different amounts. pH-sensitive gels and temperature-sensitive N-isopropylacrylamide (NIPAAm) copolymers were prepared by using some of the monomeric structures described. The pH of the swelling transition of the gels changed from 3.5 up to 9.0 as a function of the spacer length and type. The lower critical solution temperature (LCST) of NIPAAm copolymers in water was lowered from 33.6°C to 6°C as a function of the co-monomer content and type. The observed changes in the pH of the swelling transition of gels and in the LCST of NIPAAm copolymers can only be explained if hydrophobic-hydrophobic and hydrogen-bonding interactions are considered in connection with the specific chemical structure of the monomers used.     

Synthesis and characterization of thermoresponsive hydrogels cross-linked with acryloyloxyethylaminopolysuccinimide

Biodegradable cross-linkers acryloyloxyethylaminopolysuccinimide (AEA-PSI) were obtained by microwave irradiation using maleic anhydride as materials. With AEA-PSI cross-linker, cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content, thermodynamics stability, and enzymatic degradation properties were investigated. By alternating the NIPAAm/AAc molar ratio, hydrogels were synthesized to have LCST in the vicinity of 37 °C. The LCST of AEA-PSI-cross-linked P(NIPAAm-co-AAc) hydrogels was significantly influenced by monomer ratio of the NIPAAm/AAc but not by the cross-linking density within the polymer network. The water content of AEA-PSI-cross-linked P(NIPAAm-co-AAc) hydrogels was more than 90% even at 37 °C, which was controlled by the monomer molar ratio of NIPAAm/AAc, swelling media, and the cross-linking density. The thermodynamics stability was also characterized by thermogravimetry. In enzymatic degradation studies, breakdown of the AEA-PSI-cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on the cross-linking density. Submitted to Colloid and Polymer Science, 2007-1-28.     

Synthesis and characterization of thermoresponsive hydrogels cross-linked with chitosan

Hydrogels composed of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were prepared by redox polymerization with degradable chitosan cross-linkers. Chitosan degradable cross-linkers were synthesized by the acrylation of the amine groups of glucosamine units within chitosan and characterized with ¹H NMR. With the chitosan cross-linkers, loosely cross-linked poly(N-isopropylacryamideco-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content and degradation properties were investigated. The chitosan cross-linked P(NIPAAm-co-AAc) hydrogels were pliable and transparent at room temperature. The LCST could be adjusted at 32∼39°C by alternating the feed ratio. Swelling was influenced by NIPAAm/AAc monomer ratio, cross-linking density, swelling media, and temperature. All hydrogels with different feeding ratios contained more than 95% water at 25°C in the ultra pure water and phosphate-buffered saline (PBS, pH = 7.4 ± 0.1), and had a prospective swelling in the simulated gastric fluids (SGF, pH = 1.2) > 72.54%. In degradation studies, breakdown of the chitosan cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on the cross-linking density. The chitosan cross-linked P(NIPAAm-co-AAc) hydrogels which can be tailored to create environmentally-responsive artificial extracellular materials have great potential for future use.      

Synthesis of hydrophilic microspheres with LCST close to body temperature for controlled dual‐sensitive drug release

Novel stimuli‐responsive hydrophilic microspheres were prepared by free radical polymerization of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MA), as hydrophilic monomers, and N‐isopropylacrylamide (NIPAAm) and N,N′‐ethylenebisacrylamide (EBA), as thermo‐sensitive monomer and crosslinker, respectively. Hydrophilic comonomers were introduced in the macromolecular network to synthesize materials with tunable thermal behavior. In addition, by introducing in the polymerization feed both a hydrophilic and a pH‐sensitive monomer, such as MA, dual stimuli‐responsive (pH and temperature) hydrogels were synthesized. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and the shape of hydrogels was found to strictly depend on the concentration of monomers in the polymerization feed. Thermal analyses showed negative thermo‐responsive behavior with pronounced water affinity of microspheres at a temperature lower than lower critical solution temperature (LCST). In our experiment, the LCST values of the hydrogels were in the range 34.6–37.5°C, close to the body temperature, and the amount of hydrophilic moieties in the polymeric network allows to collect shrinking/swelling transition temperatures higher than the LCST of NIPAAm homopolymers. In order to test the preformed materials as drug carriers, diclofenac diethylammonium salt (DDA) was chosen and drug entrapment percent was determined. Drug release profiles, in media at different temperature and pH, depend on hydrogels crosslinking degree and drug–bead interactions. By using semi‐empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and swelling behavior of thermosensitive hydrogels based on N-substituted acrylamides and sodium acrylate

A series of hydrogels based on N-isopropylacrylamide, sodium acrylate, and N-tert-butylacrylamide were synthesized by free radical polymerization in a mixture of dioxane and water with tetra(ethylene glycol) diacrylate as the crosslinker and benzoyl peroxide as the initiator. The swelling behavior including the swelling rate of the crosslinked gels in water was studied with gravimetric method. The swelling ratio of the gel (0.1 mol% crosslinking) can reach 420 g/g at 20 °C and such a gel can release 96% of the water absorbed at 40 °C. The lower critical swelling temperature (LCST) of the copolymers can be adjusted by changing the chemical composition of the polymers. Such crosslinked gels can be potentially used as thermosensitive superabsorbent because of their high water uptake and thermal sensitivity.     

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

Macroporous temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a ⁶⁰Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300–400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.     

THERMAL-SENSITIVE BETA-CYCLODEXTRIN-CONTAINING POLY(N-ISOPROPYLACRYLAMIDE) HYDROGELS CROSSLINKED BY Si-O-Si BONDS -SYNTHESIS, CHARACTERIZATION AND PROLONGING IN VITRO RELEASE OF 5-FLUOROURACIL

A series of novel p(N-isopropylacrylamide) (PNIPAM) hydrogels were synthesized by radical copolymerization of N-isopropylacrylamide (NIPAM) and 3-methacryloxypropyltrimethoxysilane (MPTMS). The copolymers were then crosslinked through hydrolysis of the siloxane in acetic acid/water mixed solvent. Beta-cyclodextrin (Beta-CD) was introduced into the polymeric networks by condensation of 3-glycidoxypropyltrimethoxysilane derived beta-cyclodextrin (KH560-beta-CD) with MPTMS under acidic condition. These gels were heterogeneous, porous and exhibited fast deswelling kinetics when the temperature was elevated to above lower critical solution temperature (LCST). The swelling ratios of the gels containing beta-CD at room temperature were higher than that of the normal PNIPAM hydrogel, which was caused by the lower crosslinking density in beta-CD contained gels. In comparison to that of the normal PNIPAM gel, the amount of loaded-drug in the hydrogel containing beta-CD was higher, and the release time of 5-fluorouracil (5-Fu) was prolonged, which was attributed to the formation of inclusion compounds between 5-Fu and beta-CD in gel network.     

THERMAL-SENSITIVE BETA-CYCLODEXTRIN-CONTAINED POLY(N-ISOPROPYLACRYLAMIDE) HYDROGELS CROSS-LINKED BY Si―O―Si BONDS

A series of novel p（N-isopropylacrylamide） （PNIPAM） hydrogels were synthesized by radical copolymerization of N-isopropylacrylamide （NIPAM） and 3-methacryloxypropyltrimethoxysilane （MPTMS）. The copolymers were then crosslinked through hydrolysis of the siloxane in acetic acid/water mixed solvent. Beta-cyclodextrin （Beta-CD） was introduced into the polymeric networks by condensation of 3-glycidoxypropyltrimethoxysilane derived beta-cyclodextrin （KH560-beta-CD） with MPTMS under acidic condition. These gels were heterogeneous, porous and exhibited fast deswelling kinetics when the temperature was elevated to above lower critical solution temperature （LCST）. The swelling ratios of the gels containing beta-CD at room temperature were higher than that of the normal PNIPAM hydrogel, which was caused by the lower crosslinking density in beta-CD contained gels. In comparison to that of the normal PNIPAM gel, the amount of loaded-drug in the hydrogel containing beta-CD was higher, and the release time of 5-fluorouracil （5-Fu） was prolonged, which was attributed to the formation of inclusion compounds between 5-Fu and beta-CD in gel network.     

Synthesis and characterization of temperature-sensitive and biodegradable hydrogel based on N-isopropylacrylamide

Based on a biodegradable cross-linker, N-maleyl chitosan (N-MACH), a series of Poly(N-isopropylacrylamide) (PNIPAAm) and Poly(N-isopropylacrylamide-co-acrylamide) [P(NIPAAm-co-Am)] hydrogels were prepared, and their lower critical solution temperature (LCST), swelling kinetics, equilibrium swelling ratio in NaCl solution, and enzymatic degradation behavior in simulated gastric fluids (SGF) were discussed. The LCST did not change with different cross-linker contents. By altering the NIPAAm/Am molar ratio of P(NIPAAm-co-Am) hydrogels, the LCST could be increased to 39°C. The LCST of the hydrogel was significantly influenced by the monomer ratio of the NIPAAm/Am but not by the cross-linker content. In the swelling kinetics, all the dry hydrogels exhibited fast swelling behavior, and the swelling ratios were influenced by the cross-linker content and NIPAAm/Am molar ratios. Equilibrium swelling ratio of all the hydrogels decreased with increasing NaCl solution concentration. In enzymatic degradation tests, the weight loss of hydrogels was dependent on the cross-linker contents and the enzyme concentration.      

Fast responsive poly(<Emphasis Type="Italic">N,N</Emphasis>-diethylacrylamide) hydrogels with interconnected microspheres and bi-continuous structures

We prepared thermo-responsive polymer hydrogels by γ-ray irradiation of aqueous solutions of N, N-diethylacrylamide at different temperatures below and above its lower critical solution temperature (LCST). Poly(N, N-diethylacrylamide) gel had a transparent and homogeneous structure when the radiation-induced polymerization and crosslinking were carried out below the LCST (25 °C) of the polymer. On the other hand, cloudy and heterogeneous gels were formed at temperatures above the LCST of the polymer (>35 °C). From environmental scanning electron microscopy observations, the gels prepared at 35 and 40 °C were seen to show sponge-like bi-continuous porous structures, while those prepared at 50 °C showed a porous structure consisting of interconnected microspheres. For temperature changes between 10 and 40 °C, gels with porous structures showed rapid volume transitions on a time scale of about a minute, not only for shrinking but also for swelling processes, which is in remarkable contrast to the porous poly(N-isopropylacrylamide) hydrogels.     

Lower critical solution temperature control and swelling behaviour of physically crosslinked thermosensitive copolymers based on N-isopropylacrylamide

In this contribution we have developed thermosensitive polymer matrices based on N-isopropylacrylamide (NIPAAm). Preparation of the hydrogels involved photopolymerisation of a combination of NIPAAm, 1-vinyl-2-pyrrolidinone (NVP) and distilled water, in appropriate amounts and contained a UV-light sensitive initiator called 1-hydroxycyclohexylphenylketone. As NIPAAm monomer could be readily dissolved in mixtures of liquid NVP and distilled water, the use of organic solvents was not required in the polymerisation process. Furthermore, chemical crosslinking agents are not needed in the synthesis. By alternating the feed ratio, hydrogels were synthesised to have lower critical solution temperatures (LCST) in the vicinity of 37 °C. This ability to shift the phase transition temperature of the gels provides excellent flexibility in tailoring transitions for specific uses. The transition temperature of the pseudo gels was established using cloud point measurement and modulated differential scanning calorimetry (MDSC). The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (Ftir), while swelling experiments in distilled water indicate that the swelling and dissolution behaviour of the gels is strongly temperature dependent.     

Preparation and separation function of N‐isopropylacrylamide copolymer hydrogels

In this paper, N‐isopropylacrylamide (NIPA) was synthesized by acrylonitrile and isopropanol. Poly(N‐isopropylacrylamide) (PNIPA) was prepared by a chemical method. The dependence of its swelling behavior on temperature was studied. Results showed that PNIPA hydrogel was a temperature‐sensitive gel. Its LCST (lower critical solution temperature) was about 32 °C, and its swelling ratio (at 20 °C) was about 17–18. Sodium acrylate (SA) and sodium methylacrylate (SMA) were copolymerized with NIPA respectively. Equilibrium swelling ratios of the copolymer hydrogels at lower temperature were two to three times that of PNIPA. The LCST of the copolymer hydrogels could be controlled between 32 and 45 °C by adjusting the content of SA or SMA. Kinetics of P(NIPA‐co‐SA) hydrogels, whether swelling or shrinking processes, were in good agreement with apparent second order kinetic equations. Several experiments were designed to separate aqueous bovine serum albumin solution using the hydrogels prepared above. The separation efficiency was about 80%. Copyright © 2000 John Wiley & Sons, Ltd.     

新型pH及温度敏感性水凝胶

水凝胶是由三维交联网络结构的高聚物和介质共同组成的多元体系 ,因其独特的刺激响应行为 ,已在药物释放体系、物料分离、化学机械、人工肌肉等领域显示了良好的应用前景[1,2 ] .在人体体液这种复杂的环境中 ,水凝胶同时受到ｐＨ和温度等多重刺激作用 ,因此 ,研究多重响应性水凝胶具有重要意义 .聚氨酯作为一种广泛应用的高分子材料具有结构易调节、力学性能优异及生物相容性好等特点 ,在生物医学领域可将其用作假肢部件、外科用置入管、隐形眼睛等 .已有文献报道了ｐＨ敏感性聚氨酯水凝胶[3～ 5] ,但对多重响应性聚氨酯基水凝胶的报道还很…     

Versatile Pectin Grafted Poly (N-isopropylacrylamide); Modulated Targeted Drug Release

This study describes synthesis and optimization of pectin grafted poly(N-isopropylacrylamide) hydrogels as vehicles for colon-targeted theophylline model drug release. The gels were prepared in the presence of N, N′–methylenebisacrylamide (MBAA) crosslinker and ceric ammonium nitrate (CAN) initiator under N₂ atmosphere. Optimum conditions, in terms of percent of grafting (%G), were determined as follows: pectin = 1.0 g, [NIPAAm] = 26.51 mM, [MBAA] = 0.65 mM, [CAN] = 0.073 mM, polymerization temperature = 30°C and time = 4.0 h. Hydrogels were characterized by FTIR, TGA, DSC, XRD and SEM. The formed hydrogel did not have a thermo-sensitivity behavior. The in vitro percent drug release was studied in terms of different percent of grafting and different polymerization temperatures under two pH values namely 5.5 and 7.4. Conclusively, the optimum colon-targeted vehicle properties that provide the least drug release at pH5.5 and the most drug release at pH7.4 were as follows: [NIPAAm] = 26.51 mM and [MBAA] = 0.56 mM, polymerization temperature = 30°C and %G = 55.5.     

Radiation preparation and diffusion behavior of thermally reversible hydrogels

Temperature sensitive PolyNIPAAm hydrogels in the form of rod were prepared from the binary system of NIPAAm/water and ternary system of NIPAAm/Bis/water by γ-irradiation with ⁶⁰Co source at room temperature, respectively. The prepared hydrogels had obvious temperature sensitivity (LCST is about 35.0 °C) and suitable mechanical properties. The incorporation of cross-linking agent, N, N′-methylene-bisacrylamide (Bis), into the binary system of monomer/water reduced the gelation dose. The maximum swelling ratio of hydrogels was decreased with the increasing of dose or the incorporation of Bis. The diffusion behavior of water in hydrogels obtained in this work was investigated. In addition, the drug delivery of fluoro uracili (Fu-5) from the hydrogels was investigated.     

Synthesis and Properties of Hydrogels Based on Chitosan and Poly(Vinyl Alcohol) Crosslinked by Genipin

Semi‐interpenetrating polymeric networks of chitosan and poly(vinyl alcohol) [PVA] were prepared by varying the ratio of the constituents. The hydrogels were crosslinked using genipin, a naturally occurring nontoxic cross‐linking agent. The swelling behavior of these hydrogels was studied by immersing the films in deionized water at various temperatures and in buffer solutions of different pH. The states of water in the hydrogels, swollen at 25°C and pH 7, were determined using Differential Scanning Calorimetry (DSC). The swelling behavior of the gels was found to be dependent on temperature and pH of the medium. The amount of freezing water in the swollen hydrogels increased, whereas the amount of nonfreezing bound water remained more or less the same with increasing PVA concentration.