Preparation and properties of a novel thermo-responsive poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) hydrogel containing glycyrrhetinic acid

A novel thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel containing glycyrrhetinic acid(GA) was synthesized by free radical copolymerization. The structure of the product was confirmed by FT-IR and ¹H-NMR spectra. The temperature responsibility and swelling properties of the copolymerized hydrogel were investigated by differential scanning calorimetry (DSC) and gravimetric methods. The results indicated that GA-incorporated hydrogel was still temperature responsive and the swelling ratio decreased with the increasing of temperature. The lower critical solution temperature (LCST) of GA-incorporated hydrogel and poly(N-isopropylacrylamide) hydrogel was 30.00 °C and 31.21 °C, respectively, in distilled water. However, these two values were shifted to 28.22 °C and 29.16 °C in cell culture media. The novel hydrogel also exhibited reversible temperature responsibility. Deswelling kinetics indicated that the copolymerized hydrogel deswelled more rapidly than poly(N-isopropylacrylamide) hydrogel. Since GA has specific binding capacity to asialoglycoprotein receptors on the membrane of hepatocyte, this novel hydrogel with GA could be expected as good candidate for hepatic cell culture.     

Synthesis, swelling and drug release behavior of poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) hydrogel

In this study, poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) (poly(DEA-co-NHMAA)) hydrogels were synthesized by changing the initial DEA/NHMAA mole ratio, N,N'-methylenebisacrylamide and total monomer concentration. The thermosensitive and mechanical performances were optimized by altering the above parameters. The hydrogels were characterized by using Fourier transform infrared (FTIR) spectroscope and scanning electron microscope (SEM). In comparison with the PDEA hydrogel, the equilibrium swelling ratio (ESR) and lower critical solution temperature (LCST) of the hydrogels increased with the increase of NHMAA content in the feed. The swelling kinetics was also studied. The release behaviors of the model drug, aminophylline, are found dependent on hydrogel composition and environmental temperature, which suggests that these materials have potential application as intelligent drug carriers.     

Intelligent poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide)-carboxymethyl cellulose full interpenetrating polymeric networks for protein adsorption studies

Poly(N-isopropyl acrylamide) (PNIPAm)–carboxymethyl cellulose (CMC) full interpenetrating polymeric networks (IPNs), based on PNIPAm and CMC, were prepared and investigated for adsorption of biomolecules utilizing a model protein, bovine serum albumin (BSA). N-isopropyl acrylamide monomers were polymerized in the presence of a natural polymer, e.g., carboxymethyl cellulose sodium salt. N,N′-methylenebisacrylamide (CL) was used to crosslink PNIPAm and CMC chains and IPN formed simultaneously. Spectroscopic and thermal characterization of the hydrogels were done with IR spectroscopy and thermogravimetric analysis. The swelling properties of PNIPAm and PNIPAm–CMC hydrogels were investigated as functions of the medium pH, temperature, ionic strength, and BSA. It was observed that the adsorption of protein molecules onto the hydrogels was mainly dependent on temperature and pH of the environment during the experiments. The maximum adsorption capacity (X) was observed at pH 4.7 which is the isoelectric point of BSA and at 40 °C for both hydrogels; and introducing CMC to PNIPAm increased the protein adsorption of the hydrogel. Adsorbed amounts of BSA were 26.70 mg g⁻¹ (4 °C) and 38.70 mg g⁻¹ (40 °C) for PNIPAm–CMC full IPN hydrogels. Adsorbed BSA (up to 80%) was eluted in the elution medium containing 0.1 mol dm⁻³ NaSCN at pH 8.0. Synthesized cylindrically shaped PNIPAm–CMC full IPN hydrogels can be used for adsorption studies related to the removal of proteins in pH- and temperature-sensitive biotechnological areas.     

Synthesis and characterization of mesoporous silica/poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) functional hybrid useful for drug delivery

Recent studies indicate the use of mesoporous silica and polymeric sensitive hydrogels as suitable for drug delivery systems due to their specific characteristics. Polymeric hydrogels, such as poly(N-isopropylacrylamide) [P(N-iPAAm)], show volumetric expansion/contraction behaviour at 306 K, which that can be used to develop a thermosensitive drug delivery system. In this study, we report a facile and direct synthesis route to obtain hybrid functional nanosystems based on silica-P(N-iPAAm) by using a neutral surfactant and without any functionalization method and the assessment of its release rate of a model drug. The materials were characterized by Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy, transmission electron microscopy and thermal analysis. A release assay with atenolol monitored by UV–Vis spectroscopy was performed for pure SBA-15 and a hybrid system at different temperatures in order to evaluate the influence of the thermosensitive behaviour of the polymer on the release kinetics. The response of the hybrid system as a drug delivery device is influenced by the volumetric contraction of P(N-iPAAm) up to the lower critical solution temperature (LCST) due to phase transition. Above the LCST, drug release depends essentially on the temperature.     

温度/pH敏感性Semi-IPN水凝胶的制备与性能

以N-乙烯基乙酰胺（NVA）、醋酸乙烯酯（VAc）和甲基丙烯酸-N,N′-二甲氨基乙酯（DMAEMA）为原料,通过自由基聚合制备了PDMAEMA/P（NVA-co-VAc）半互穿网络（Sem-iIPN）水凝胶。实验结果表明,该水凝胶具有较好的温度敏感性、pH敏感性、溶胀-退胀可逆性。随着温度的逐渐升高,凝胶的溶胀率随之...     

The synthesis,swelling behaviour and rheological properties of chemically crosslinked thermosensitive copolymers based on <Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide

In this contribution thermosensitive polymer matrices based on N-isopropylacrylamide have been developed. The hydrogels were prepared by photopolymerisation of N-isopropylacrylamide and 1-vinyl-2-pyrrolidinone in appropriate amounts of distilled water. The monomers were cured using a UV-light sensitive initiator called 1-hydroxycyclohexylphenylketone. These copolymers were crosslinked using ethylene glycol dimethacrylate and poly(ethylene glycol) dimethacrylate with molecular weights 600 and 1,000, at 0.1 wt% of the total monomer content. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR) and the transition temperature of the hydrogels was determined using modulated differential scanning calorimetry (MDSC). By altering the feed ratio, hydrogels were synthesised to have lower critical solution temperatures (LCST) around 37 °C. This ability to shift the phase transition temperature of the gels provides excellent flexibility in tailoring transitions for specific uses. The samples synthesised with PEG1000DMA crosslinking agents absorbed over 18 times their weight in water, while maintaining good gel integrity thus falling marginally short of being characterised as superabsorbent. Each of the samples showed similar deswelling behaviour at 37 °C. Rheological studies showed that increasing the molecular weight of the crosslinking agent caused an increase in hydrogel strength.     

Stimuli-responsive chitosan/poly (<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) semi-interpenetrating polymer networks: effect of pH and temperature on their rheological and swelling properties

The aim of this work was to synthesize semi-interpenetrating polymer networks (semi-IPNs) by free radical polymerization of N-isopropylacrylamide [poly (NIPAAm)], in the presence of chitosan (CHI), and to study the effect of pH and temperature changes on their rheological and swelling properties. The semi-IPNs are thermally stable up to about 400 °C and the presence of CHI increases the thermal degradation rate compared to bare poly (NIPAAm). The prepared systems presents a well-defined porosity and proved to be non-toxic, in vitro, on human embryonic skin fibroblast, thus offering appropriate support for cell proliferation. The semi-IPNs present, at physiological pH, swelling degrees well below those of the pure poly (NIPAAm). Differently, at acidic pH, the CHI macromolecules are protonated and become much more permeable to the diffusion of water giving a swelling degree that approaches that of bare poly (NIPAAm). The viscoelastic moduli of the semi-IPNs increase as a function of pH while the LCST remain unchanged. Moreover, the semi-IPNs viscoelastic moduli increase with the increase of CHI content and, in particular, the difference between the elastic modulus before and after the sol/gel transition is higher for the semi-IPN than for bare poly (NIPAAm) just at about physiological conditions.     

Synthesis and characterization of a thermo-sensitive poly(<Emphasis Type="Italic">N</Emphasis>-methyl acryloylglycine methyl ester) used as a drug release carrier

In this article, poly(N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by ¹H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers (N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.     

The effect of salts and pH buffered solutions on the phase transition temperature and swelling of thermoresponsive pseudogels based on <Emphasis Type="Italic">N-</Emphasis>isopropylacrylamide

The temperature sensitive nature of poly(N-isopropylacrylamide) makes it an attractive candidate for controlled drug delivery devices. A series of temperature responsive poly (N-isopropylacrylamide)-polyvinyl pyrrolidinone random copolymers were produced by free radical polymerisation using 1-hydroxycyclohexylphenyketone as a UV-light sensitive initiator. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR). The copolymers possess a lower critical solution temperature (LCST) in pure water, but the transition temperature may be affected by the addition of various cosolutes. The LCST of the pseudogels (physically crosslinked gels) was investigated in distilled water and a variety of salt and pH buffer solutions, using modulated differential scanning calorimetry (MDSC) and rheological analysis. The pH buffer solutions prepared mimic the variety of conditions encountered by drug delivery systems administered orally. The pH effects on the LCSTs of the temperature sensitive gels appear not obvious; while the salts used to prepare the pH buffer solutions have a more notable effect (‘salting out effect’) on the phase transition temperature. All swelling studies were carried out on the hydrogels at 37°C in distilled water, pH buffer 1.2 and pH buffer 6.8. The swelling/dissociation behaviour of the gels is found to be highly dependent on the pH buffer solution used, as the salts incorporated in preparing the pH buffer solutions lowers the phase transition of the copolymers to below the test temperature of 37°C, thus making them less soluble.     

Thermoresponsive poly(<Emphasis Type="Italic">N</Emphasis>-vinylcaprolactam) cryogels: synthesis and its biophysical evaluation for tissue engineering applications

The thermoresponsive poly(N-vinylcaprolactam) (PVCl) based cryogel network were synthesized and characterized with respect to physical and biological properties. The PVCl cryogel crosslinked with polyethylene glycol-diacrylate (PEGda) was synthesized in 1% dimethyl sulfoxide containing aqueous medium at −12°C for 12–14 h. The cryogel synthesized in this manner were highly spongy in nature and can absorb water in its porous network. These polymeric cryogel networks have good physical morphology as confirmed by scanning electron microscopy. The estimated porosity of these cryogels was 90% as demonstrated by various methods based on absorption of water and cyclohexane. The median pore diameter and surface area was 30 μm and 2.0253 m²/g, respectively as confirmed by analysis on mercury porosimeter. These materials can interact with biological system without any cytotoxic effects. Change in temperature influenced the adsorption of fetal bovine serum (FBS) on PVCl scaffold which showed maximum protein adsorption at 37°C, as compared to that at 25°C. Furthermore, the fibroblast cell adhesion studies showed the potential of these PVCl based cryogels as tissue engineering scaffolds.     

Temperature swing adsorption of melamine on thermosensitive poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) cryogels

In the past few years, polymer-based adsorbents have been emerging as highly effective alternatives to activated carbons for pollutants removal and recovery from industrial effluents. In this article, novel thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) cryogels adsorbents were directly prepared with N-isopropylacrylamide (NIPAAm) as a thermosensitive monomer and PEG-20,000 as a porogen at −12 °C by means of an in situ free-radical redox cryopolymerization. Subsequently, PNIPAAm cryogels were further employed to adsorb and desorb melamine through temperature swing adsorption (TSA) between 25 and 50 °C. The adsorption isotherms were correlated to Langmuir and Freundlich isotherm models. Moreover, the result indicated that the developed PNIPAAm cryogels adsorbents could be utilized effectively to concentrate melamine from aqueous solutions and spiked liquid milk. The cycle of the adsorption and desorption could be repeated without much loss of the melamine adsorbing ability.     

Poly (pyrrole-co-<Emphasis Type="Italic">N</Emphasis>-methyl pyrrole) for application to cholesterol sensor

Cholesterol oxidase (ChOx) has been electrochemically entrapped onto p-toluene sulphonate (PTS) doped poly (pyrrole-co-N-methyl pyrrole) (1:1) on indium-tin-oxide (ITO) glass plates. This ChOx-copolymer-PTS/ITO bioelectrode has been characterized using cyclic voltammetry (CV), Fourier transform infrared (FTIR) spectroscopy, UV-visible spectroscopy, scanning electron microscopy (SEM) techniques. The cholesterol bioelectrode shows response time of 19 s, linearity from 50 to 400 mg/dL as a function of cholesterol concentration. It exhibits optimum pH range between 6.5 and 7.5, shelf-life of up to 6 weeks at 4 °C and shows almost undisturbed response in presence of interferents like ascorbic acid, uric acid and glucose.     

Effect of the molecular weight of polyethylene glycol (PEG) on the properties of chitosan-PEG-poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) hydrogels

Our prior study has shown that polyethylene glycol (PEG) played a crucial role in improving the properties of the physically crosslinked chitosan-PEG-poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. In this paper, we further investigated the effect of the molecular weight (MW) of PEG on the properties of the chitosan-based physical hydrogels. Fourier Transform Infrared Spectroscopy (FTIR) study showed that the interaction between PEG and other components in the physically crosslinked hydrogels became stronger as the MW of PEG increased. The wide angle X-ray diffraction (WAXD) study indicated that the crystallinity of the physical hydrogels decreased with an increase in the MW of PEG. The thermal study using differential scanning calorimetry (DSC) revealed the crystallizability of the physical hydrogels first reduced with an increase in the MW of PEG, but slightly increased thereafter with a further increase in the MW of PEG. The swelling test showed the water uptake capability of the physical hydrogels increased with an increase in the MW of PEG. The results obtained by scanning electron microscope (SEM) found that the morphological changes of the physical hydrogels with MW of PEG were consistent with the results of swelling and thermal properties; and, contrary to pure PNIPAAm hydrogels which showed a compact and dense network structure at a temperature (37 degrees C) above its LCST, the physical chitosan-PEG-PNIPAAm hydrogels exhibited porous network structure at 37 degrees C instead. The mechanical property of the physical hydrogels was initially increased with an increase in PEG MW, but deteriorated with a further increase in PEG MW. Therefore, the MW of PEG played a key role in controlling the property of the chitosan-based physical hydrogels.     

The pH-induced thermosensitive poly (NIPAAm-<Emphasis Type="Italic">co</Emphasis>-AAc-<Emphasis Type="Italic">co</Emphasis>-HEMA)-<Emphasis Type="Italic">g</Emphasis>-PCL micelles used as a drug carrier

The macromonomer of 2-hydroxyethyl methyacrylate-caprolactone (HPCL) was synthesized by the ring-opening polymerization (ROP) of ε-caprolactone, which was initiated by 2-hydroxyethyl methyacrylate (HEMA). Then, the graft terpolymers of NIPAAm-co-AAc-co-HEMA-g-PCL (PHNA-CL) with varying mole ratios were subsequently synthesized by free radical polymerization of HEMA-PCL, N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc). PHNA-CL was further self-assembled in different types of solvent. All the as-prepared copolymers were characterized by ¹H NMR, FT-IR and GPC. Micellization behaviors of micelles were studied by TEM and DLS. The micelles exhibited a phase transition temperature which can be readily adjusted by changing pH value of the micellization system. Micelle loaded with doxorubicin (DOX) was used to evaluate the drug release behavior. The release of DOX from micelles could be controlled by changing pH value and temperature in buffer solutions. The micelles are potentially to be used as a new anticancer drug carrier for intracellular delivery.     

Cell attachment/detachment behavior on poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide)-based microgel films: the effect of microgel structure and swelling ratio

Microgels are cross-linked soft particles with a three-dimensional network structure that are swollen in a good solvent. Poly(N-isopropylacrylamide) (pNIPAAm)-based microgels have attracted great attentions for their temperature responsive property, particularly in recent years, pNIPAAm-based microgel films were utilized as a new kind of thermoresponsive surface to tune cell attachment/detachment behavior via temperature stimuli. However, some results are not consistent, for example, different polymerization conditions may bring out different results even for pure pNIPAAm microgel. This work aims to find out which factor plays the critical role for successful cell detachment on the pNIPAAm-based microgel films. The results unraveled that the structure and swelling ratio of the microgel rather than the film thickness plays a key role on the successful cells detachment, unlike linear pNIPAAm films in which the cells’ attach/detach property is only determined by the film thickness. For poly(N-isopropylacrylamide–styrene) microgel film, NIH3T3 cells could only detach when the microgel has a uniform structure and the volume dilatation of the microgel (20/38 °C) is larger than 4.     

Drug release behaviors of a pH/temperature sensitive core-shelled bead with alginate and poly(<Emphasis Type="Italic">N</Emphasis>-acryloyl glycinates)

In this study, a pH/temperature sensitive bead with core-shelled structure, as a drug carrier, was prepared by grafting of N-acryloylglycinates on the surface of sodium alginate beads. The pH and temperature sensitivity of the beads originate from sodium alginate (SA) and copoly(N-acryloylglycinates), respectively. Here, indomethacin (IMC) was selected as a drug model molecule and loaded in SA beads. The release of IMC was systematically investigated as a function of temperature, pH, and SA concentration. The amount of IMC released from beads was as high as 61.6%in pH = 7.4 phosphate buffer solution (PBS) over 620 min, whereas only 27.9% IMC diffused into the pH = 2.1 PBS. In addition, the release rates of IMC at 37.5°C were faster than that at 20.0°C and decreased with increasing SA concentration in the beads. The result indicates that the sensitive beads have the potential to be used as an effective pH/temperature-controlled delivery system in the biomedical fields.     

Evaluation of electrospun nanofiber formation of perfluorosulfonic acid and poly (<Emphasis Type="Italic">N</Emphasis>-vinylpyrrolidone) through solution rheology

Electrospinning performance of 5–52 wt% perfluorosulfonic acid (PFSA), poly (N-vinylpyrrolidone) (PVP), and PFSA/PVP blends in N,N-dimethylformamide (DMF) with various PFSA/PVP ratios were systematically investigated in respective of solutions properties, mainly surface tension and rheological properties. Mechanical relaxation time τ _M calculated from rheological results happens to be closely correlated with nanofiber morphology, and is used to evaluate the electrospinnability. Polymer solutions with higher τ _M show better electrospinnability. Morphologies of the electrospun samples were observed by Scanning electronic microscopy. The results show that the pure PFSA solutions, even with a quite high concentration up to 52 wt%, fail to be electrospun and possess a very low τ _M. Addition of PVP improves electrospinnability of PFSA and increases τ _M. The electrospinnability of PFSA/PVP/DMF solutions can be manipulated by changing the ratio of PFSA to PVP and the total polymer concentration of the mixed solutions. The PFSA nanofiber mats with a small fraction of PVP (<8 wt%) with the average diameter of 370 nm were successfully obtained.     

Evaluation of hydrogels for soft tissue adhesives <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> analyses

In this study, natural materials (sodium alginate, dextran, gelatin and carboxymethyl chitosan) were modified to get aldehyde components and amino components. Upon mixing the two-component solutions together, four kinds of Schiff base hydrogels formed successfully within 5-300 s and could seal the wound tissue. The cytotoxicity tests of hydrogel extraction solution confirmed that the hydrogels are nontoxic materials. The adhesive ability was evaluated in vivo by measuring the adhesive strength after sealing the skin incisions on the back of rats. All the hydrogels showed higher adhesive strength than that of commercial fibrin glue and the blank control. The histological staining observation by hematoxylin and eosin staining (HE) and Masson’s trichrome staining (MTC) methods suggested that the hydrogels had good biocompatibility and biodegradation in vivo. They have only normal initial inflammation to skin tissue and could improve the formation of new collagen in the incision section. So, the prepared hydrogels were both safe and effective tissue adhesive, which had the great potentials to be used as skin tissue adhesive.     

Preparation and properties of a drug release membrane of mitomycin C with <Emphasis Type="Italic">N</Emphasis>-succinyl-hydroxyethyl chitosan

A novel drug loaded membrane made of N-succinyl-hydroxyethyl chitosan and mitomycin C was used as an implant for glaucoma filtering surgery. The characteristics of the membrane, such as FTIR, equilibrium water content, swelling ratio, permeability, and drug release in vitro were determined. The L929 fibroblast inhibition of drug loaded membranes was compared to hydroxyethyl chitosan film and blank control, detecting by MTT. The biodegradability and biocompatibility were evaluated by implanting membranes into the subcutaneous tissue and muscle of rats. FTIR indicated mitomycin C was introduced. The experimental results indicated the drug loaded membrane was effective on the swelling property, permeability, and drug release in vitro. Cell culture experimental results demonstrated that the destination membrane inhibited fibroblast proliferation. In vivo, the membranes showed bioabsorption and biocompatibility. The experimental results provide a theoretical basis for the future development of the drug loaded membrane as an implant for increasing the success rate of filtering surgery.     

Synthesis and properties of <Emphasis Type="Italic">O</Emphasis>-carboxymethyl chitosan/methoxy poly(ethylene glycol) graft copolymers

O-carboxymethyl chitosan/methoxy poly(ethylene glycol) graft copolymers (OCMCS-g-MPEGs) with different degrees of substitution (DS) were synthesized by reductive N-alkylation of chitosan with poly(ethylene glycol) aldehyde. The properties of OCMCS-g-MPEGs, including the solubility, structure, hydrodynamic behaviors, isoelectric point (IEP) and interaction with water-soluble chitosan, were investigated. As a PEGylated polyampholyte, OCMCS-g-MPEGs can resolve in water over all pH range and the pH value at IEP (pH_IEP) decreases when DS increases. The hydrodynamic behaviors of OCMCS-g-MPEGs in deionized H₂O are markedly affected by DS and pH_IEP in the experiment concentration range. The particle size of the complexes of OCMCS-g-MPEGs with water-soluble chitosan is strongly affected by the concentration of water-soluble chitosan and the pH value.