A novel positively thermo-sensitive hydrogel based on ethylenediaminetetraacetic dianhydride and piperazine: Design, synthesis and characterization

A new positively thermo-sensitive hydrogel was designed and synthesized by a condensation polymerization reaction of ethylenediaminetetraacetic dianhydride（EDTAD） and piperazine（PA） to give poly（ethylenediaminetetraacetic dianhydride-copiperazine） （PEP）.The obtained polymers’ structure was characterized by FTIR and ¹³C NMR.The backbone of the polymer linked by amide bond and abundant of carboxyl groups as pendant group could form strong intermolecular and intramolecular hydrogen bond at lower temperature and dissociate at higher temperature,resulting in the polymer with thermo-sensitivity.The aqueous solution of PEP at lower temperature（<20℃） showed micro-gel formation and transformed to transparent solution at higher temperature（>40℃）.Transition temperature shifted to higher value with the increasing of concentration.The hydrogel exhibited reversible phase transition and the transmittance change was not weakened by multiple temperature changes.     

Novel amphoteric pH-sensitive hydrogels derived from ethylenediaminetetraacetic dianhydride, butanediamine and amino-terminated poly(ethylene glycol): Design, synthesis and swelling behavior

Novel amphoteric pH-sensitive hydrogels with pendant carboxyl and backbone tertiary amine groups were designed and synthesized. First, ethylenediaminetetraacetic dianhydride (EDTAD) reacted with butanediamine (BDA) via N-acylation reaction to give a polyamide prepolymer with pendant carboxyl groups (PEB–COOH); then amino-terminated poly(ethylene glycol) 500 (ATPEG500) was added as a cross-linking agent to produce the desired network polymer (PEB–ATPEG500–COOH). The obtained hydrogels are potentially degradable and non-toxic since its backbone and cross-linking sections are both linked by amide bonds and all monomers have been proved as safe. FTIR, ¹H NMR, ¹³C NMR and ninhydrin reaction method were employed to qualitatively and quantitatively characterize the obtained polymers. The effect of cross-linking agent amount, characterized by the molar ratios (R_m) of NH₂ groups in ATPEG500 to pendant COOH groups in PEB–COOH, on the swelling behavior of the proposed hydrogel was examined. The results indicate that the equilibrium swelling ratio decreases and the pH-sensitivity becomes retarded with the increase of R_m. For PEB–ATPEG500–COOH hydrogels with R_m no more than 0.42, they exhibited three SR_e variation zones at pH 2–4, pH 6–7 and pH 9–11, respectively, suggesting obvious and interesting amphoteric pH-sensitivity. In addition, the swelling kinetics tests on PEB–ATPEG500–COOH with R_m = 0.32 reveal that the swelling kinetics of proposed hydrogel follows a Fickian diffusion process in media of pH 7, and an anomalous diffusion process in media of pH 2 and 11. The above obtained results will facilitate the application of this proposed hydrogel in biomedical fields, particularly in the drug controlled release.     

Preparation and characterization of temperature- and pH-sensitive hemicellulose-containing hydrogels

In this work, a hemicellulose-containing hydrogel was synthesized. As the first step, a temperature- and pH-sensitive copolymer was synthesized from itaconic acid and N-isopropylacrylamide (NIPAAm). Then the hydrogel was prepared by reacting the copolymer with acylated hemicellulose and polyvinyl alcohol. The morphology, compressive strength, thermal stability, swelling/deswelling behavior, drug-release behavior performances of the hydrogels were investigated. The lower critical solution temperature of the hydrogels varied in 34–44°C when the NIPAAm and itaconic acid mass ratios ranged in 100/0–90/10. Both temperature and pH had a significant influence on equilibrium swelling ratio of hydrogels. The equilibrium swelling ratio increased with pH, but decreased with temperature. Cytocompatibility assay demonstrated that this hemicellulose-containing hydrogel was biocompatible. The release process of salicylic acid suggested that this hydrogel had a potential use in controlled drug release.     

A pH-sensitive Modified Polyacrylamide Hydrogel

Intelligent hydrogels which have the capability to respond to small external stimulus changes, such as temperature1, pH2, photo field3, and antigen4, have attracted significant attention from both academia and industry. pH-sensitive polymers are produced …     

温度及pH值敏感水凝胶的合成和应用

直接将丙烯酸单体与N-异丙基丙烯酸胺共聚交联合成了温度及pH值敏感的水凝胶。包埋于水凝胶中的药物的释放随温度升高和pH值增大而加快，药物的释放兼有温度和pH值敏感性，对pH值的响应更加显著。     

Synthesis and characteristic of the thermo- and pH-sensitive hydrogel and microporous hydrogel induced by the NP-10 aqueous two-phase system

A series of novel thermo- and pH-sensitive (NP10-AA TPS) hydrogels and microporous (NP10-AA MP) hydrogels, inducing by polyoxyethylene (10) nonyl phenyl ether (NP-10) aqueous two-phase system, was designed and fabricated with acrylic acid (AA) as the monomer for the first time. The resultant NP10-AA TPS hydrogel, compared with the traditional TPS hydrogel, was more advanced in both of the high swelling ratio and the variable lower critical solution temperature (LCST). A simple synthesis technique of the NP10-AA MP hydrogel was developed. The thermo-sensitivity of the NP10-AA TPS hydrogel including the initial swelling ratio, LCST, dehydrated efficiency, was depended strongly on the crosslinker (MBA), initiator (APS), NP-10 and AA concentration. The swelling rate of the NP10-AA MP hydrogel was much higher than that of AA hydrogel dehydrated in the same lyophilization condition.     

Synthesis and characterization of a pH-sensitive shielding system for polycation gene carriers

To increase the in vivo stability of polycation gene carriers,a pH-sensitive shielding system,γ-benzyl L-glutamate-co-glutamate acid polymer(PGA(60)(60 refers to the molar ratio of glutamate acid in the polymer)),was synthesized and characterized.PGA(60) showed pH sensitivity at about pH 6.0.PGA(60) shielded the positive charge of DNA/PEI(1:1) complexes.Gel retardation assay showed that no DNA-strand exchange with PGA(60) occurred after PGA(60) was added to DNA/PEI complexes at different proportions.MTT cyt...     

Synthesis and properties of a novel double network nanocomposite hydrogel

A novel polyacrylamide/polyacrylic acid (PAAm/PAA) double network (DN) nanocomposite (NC) hydrogel had been synthesized by two‐step solution polymerization. The PAAm network was crosslinked by inorganic clay while the PAA network was crosslinked by a chemical crosslinker. The chemical structure of the network was confirmed by Fourier transform infrared (FTIR), X‐ray diffraction (XRD), and transmission electron microscopy (TEM). The swelling and mechanical strength properties of PAAm/PAA hydrogels were examined. The results showed that a DN hydrogel achieved both a high swelling capacity of 1219 g/g in deionized water and 124 g/g in 0.9 wt% NaCl solution and high compressive stress of 21.5 kPa in a high water content of 99.58%. Copyright © 2008 John Wiley & Sons, Ltd.     

A novel amphiphilic pH-sensitive hydrogel based on pullulan

Novel polyelectrolyte and amphiphilic hydrogels based on pullulan have been prepared using 1-ethyl-3-[3-(dimethylamino)-propyl]carbodiimide hydrochloride and N-hydroxysuccinimide. The cross-linking reaction is fast and lead to zero length ester cross-links by the reaction of a carboxylate group with an alcohol function of the polysaccharide. The charge density and the hydrophobic rate of the precursor carboxymethylpullulan (CMP) are controlled during the carboxymethylation of pullulan and the grafting reaction of octyl chains on CMP, respectively. The grafting degree influences the conformation of the hydrophobically modified CMP (HMCMP) in solution and leads to the formation of hydrophobic clusters firstly in the HMCMP solutions and further in the HMCMP hydrogels. The swelling measurements of HMCMP hydrogels at different salt concentrations (0–0.2 M NaCl) and different pH (3–11) shows the ionic strength and pH sensitivity of the gels. The loading of a hydrophobic probe molecule can be controlled by the grafting degree of HMCMP hydrogels.     

Synthesis, characterization and swelling properties of a chemically cross-linked poly(vinyl alcohol) hydrogel

A poly(vinyl alcohol) hydrogel was prepared by coupling poly(vinyl alcohol) with epichlorohydrin as the cross-linking agent. The structure of the hydrogel was characterized by FTIR and GPC techniques. Various amounts of water were added into the dry gel to swell it, and the quantity of water in various states in the partially swollen hydrogel was determined by DSC technique. The analytical results indicate that the water introduced into the dry gel first combines with the hydrophilic groups of the network chains through hydrogen bond forming non-freezable water. The weight ratio of the non-freezable water to dry gel in the hydrogels is about 0.20. After the non-freezable water is saturated, the additional water penetrates the network space and exists simultaneously both in the freezable and free water states until reaching equilibrium swelling. Translated from Acta Polymeric Sinica, 2006, (5): 671–675 (in Chinese)     

PVA/PAA thermo-crosslinking hydrogel fiber: preparation and pH-sensitive properties in electrolyte solution

The preparation of thermo-crosslinking hydrogel fibers composed of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) was presented. The hydrogel fiber was prepared by extruding the spinning dope from in situ polymerization of acrylic acid in the presence of PVA into coagulating bath of saturated ammonium sulfate aqueous solution. The network was formed by thermally heating the dried fibers under vacuum. The final hydrogel fibers exhibit pH-sensitive behavior and show hysteresis loop in the pH range from 2.5 to 12.5. The pH value at which the swelling ratio of the fiber had a jump shifted to lower value with increasing the PAA content within the network. Increasing the heating temperature and time for the fibers, the swelling ratio decreased and the jump point pH shifted to higher pH value. The oscillatory swelling/contracting behavior of the hydrogel fiber exhibited a well reversible pH-responsive property.     

Preparation and characterization of a novel pH-sensitive ion exchange resin

Methylacrylic acid/styrene cross-linked with divinylbenzene is a novel pH-sensitive ion exchange resin. Microspheres of this resin were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The microspheres showed a pulsatile swelling behavior when the pH of the media changed. The pH-sensitive microspheres were loaded with salbutamol sulfate and the drug-release characteristics were studied under both simulated gastric and intestinal pH conditions. The results obtained showed that the drug release also depended on the pH of the release media.     

Synthesis and properties of a temperature-sensitive chelating hydrogel and its metal complexes

A temperature-sensitive chelating hydrogel was synthesized by the copolymerization of 1-(β-acrylamidoethyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (AHMP) and N-isopropylacrylamide (NIPAA) in the presence of N,N' -ethylene-bis-acrylamide as a crosslinking agent. The AHMP-NIPAA hydrogel formed a red complex with iron(III) and a pale green complex with Cu(II), respectively. It was observed that the hydrogel and its metal complexes had a high swelling ratio below the temperature of 35°C, while above that temperature the swelling ratios were dramatically decreased. Furthermore, the swelling ratio of the metal complexes was much lower at the swelling temperature (below 35°C) than that of the hydrogel itself, which might be due to the lower flexibility of the complexes. The iron(III) chelating study showed that the hydrogel had a high chelating efficiency at its swelling temperature, while the chelating efficiency of the hydrogel was very low at its deswelling temperature (>35°C). It was found that the chelating efficiency depended on the swelling ratio of the hydrogel in water, which could be explained by the difference in contactable internal surfaces at different temperatures. The hydrogel and its metal complexes could be easily separated at their deswelling temperature. It was also convenient to regenerate the hydrogel with 1 M HCl for reuse.     

A new type of pH-sensitive phospholipid

We describe the synthesis and characterization of a type of pH-sensitive pentaerythritol phospholipids, using a trialkoxybenzylidene acetal as the acid-labile moiety. This lipid was prepared by an eight-step synthesis via a latentiation strategy. Liposomes were prepared via the thin film extrusion method. The changes of liposomal sizes were measured by dynamic light scattering. Content release rates of the liposomes as a function of pH were monitored by using a calcein fluorescence dequenching assay. These results indicated that this new liposomal system was capable of releasing its contents under mildly acidic conditions. At last, in vitro cytotoxicity was assayed against three cell lines, suggesting this type of phospholipids was low toxic.     

Ultrasonic-enhanced synthesis of rubber-based hydrogel for waste water treatment: Kinetic,isotherm and reusability studies

Hydrogel is used as an adsorbent for the removal of dyes and heavy metals in waste water. In this work, different methods of synthesising novel hydrogels from liquid natural rubber (LNR) were investigated. The two different methods were ultrasonic-assisted polymerisation and heating under reflux. Through graft modification, LNR had initially combined with maleic anhydride (MaH) using benzoyl peroxide (BPO) as a radical initiator. After grafting, acrylic acid (AA) was crosslinked onto LNR-g-MaH using N,N-methylenebisacrylamide (MBA) and potassium persulfate (KPS) as a crosslinker and initiator, respectively. The best method between the two different techniques was identified via a five-level-two-factor response surface methodology (RSM). Higher adsorption percentage (93.34%) was observed in the ultrasonic technique. Meanwhile, the effects of adsorbent mass, dye concentration, pH solution and ionic strength were also investigated and results showed that different conditions were found to give different MG dye adsorption rates. The adsorption of MG dyes on hydrogel is dependent on pH and ionic strength solution. This action indicates an ion exchange mechanism. From an isotherm study, it was found that the Freundlich isotherm best fitted the adsorption of MG dyes. Furthermore, the adsorption kinetic data followed the pseudo-second order kinetic model and the reusability of hydrogel was also investigated.     

Frontal polymerization synthesis and characterization of temperature- and pH-sensitive hydrogels

The temperature- and pH-sensitive hydrogels, poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AAc)), were synthesized via frontal polymerization (FP). The reaction components have been varied in order to find their influences on frontal parameters and copolymer features. The results showed that front velocity and front temperature were dependent on the initiator concentration, reactant dilution, and NIPMA/AAc molar ratio. In addition, the morphology and sensitive behavior of the FP hydrogels were mainly affected by monomers’ ratio. Namely, the pore size, swelling abilities, LCST, and response kinetics of copolymer hydrogels obviously increased with the increasing acrylic acid concentration; however, they slightly changed with varying of amounts of initiator and solvent. Finally, in comparison with the hydrogels prepared by conventional batch polymerization, the ones synthesized by frontal polymerization exhibited more homogeneous chain composition and improved microstructure and response ability.     

Radiation preparation and characterization of pH-sensitive hydrogel of acrylic acid/cyclodextrin based copolymer

A β-cyclodextrin (β-CD) based monomer (MAH-β-CD) containing vinyl and carboxyl functional groups was synthesized by reaction of β-CD with maleic anhydride (MAH). A novel hydrogel, poly(AAc-co-MAH-β-CD) with pH and ionic strength sensitivities, was prepared by irradiating the aqueous solution mixture of acrylic acid (AAc) and MAH-β-CD with electron beam. The effect of the feed ratio of the components and irradiation dose on the swelling and deswelling properties of the hydrogel was studied, respectively, the effect of pH and ionic strength on the swelling ratio was determined. Experimental results showed that these copolymer hydrogels did not show any noticeable change in swelling ratio at lower pH range (pH 1–3). However they showed an abrupt increase in swelling ratio at the range of pH 3–6, due to the ionization of carboxyl groups. Fourier transform infrared (FT-IR) spectrometer was applied in the attenuated total reflectance (ATR) mode for analyzing the structure change of the hydrogels after the treatment of different pH buffer solutions.     

Design, synthesis and biological characterization of novel inhibitors of CD38

Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca(2+) messenger molecule, cyclic ADP-ribose, from NAD(+). It is well established that this novel Ca(2+) signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD(+) complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound 1-14). A number of these compounds exhibited moderate inhibition of the NAD(+) utilizing activity of CD38, with Compound 4 showing the highest potency. The crystal structure of CD38/Compound 4 complex and computer simulation of Compound 7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds 4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development.     

Design of a rate- and time-programming drug release device using a hydrogel: pulsatile drug release from κ-carrageenan hydrogel device by surface erosion of the hydrogel

We have found that a repetitive pulsatile drug release with a certain time interval is observed from a monolithic hydrogel device by surface erosion of the hydrogel. As a model system of pulsatile drug release, dibucaine hydrochloride and κ-carrageenan hydrogel were chosen as a drug and a device, respectively. Electrostatic interactions between dibucaine hydrochloride and κ-carrageenan polymer segments are strong, since dibucaine hydrochloride is positively charged and each disaccharide repeating unit of κ-carrageenan chains has one sulfate group. Dibucaine hydrochloride was loaded into the hydrogel by immersing dry κ-carrageenan hydrogel disks in a dibucaine hydrochloride solution for 24 h. The pulsed release of dibucaine hydrochloride from the device was observed every 50 min between 30 and 250 min after the release starts. The weight of κ-carrageenan hydrogel decreases in an oscillatory manner with time in distilled water. The oscillatory changes observed in the hydrogel weight in distilled water are considered to be caused by influx and efflux of water molecules into and from the surface and core of the hydrogel and by polymer liberation from the hydrogel. This phenomenon was well explained by our kinetic model [Colloids and Surfaces B 8 (1996) 93–100]. The time interval between pulses observed in drug release coincides with that observed in the oscillatory weight change of the hydrogel. From these, it was concluded that the pulsatile release of dibucaine hydrochloride from the device was caused by the pulsatile liberation of swollen κ-carrageenan hydrogel from the surface of the device.     

Preparation of a novel pH-responsive silver nanoparticle/poly(HEMA-PEGMA-MAA) composite hydrogel

In this paper, series of novel pH-responsive silver (Ag) nanoparticle/poly(2-hydroxyethyl methacrylate (HEMA)-poly(ethylene glycol) methyl ether methacrylate (PEGMA)-methacrylic acid (MAA)) composite hydrogel were successfully prepared by in situ reducing Ag⁺ ions anchored in the hydrogel by the deprotonized carboxyl acid groups. X-ray diffraction (XRD), UV-vis spectrophotometry, transmission electron microscopy (TEM) and electric conductivity tests were used to characterize the composite system. It was found that the size and morphology of the reduced Ag nanoparticles in the composite hydrogels could be changed by loading the Ag⁺ ions at various swelling ratios of hydrogel. Moreover, compared to the pure poly(HEMA-PEGMA-MAA) hydrogel, not only did the Ag nanoparticle/poly(HEMA-PEGMA-MAA) composite hydrogels exhibit much higher swelling ratio and faster deswelling rate, but also higher pH switchable electrical properties upon controlling the interparticle distance under pH stimulus. The pH responsive nanocomposite hydrogel reported here might be a potentially smart material in the range of applications including electronics, biosensors and drug-delivery devices.