Thermoresponsive poly (N-vinylcaprolactam)-g-galactosylated chitosan hydrogel: synthesis,characterization, and controlled release properties

Abstract

A dual (thermo- and pH-) responsive hybrid copolymer, poly(N-vinylcaprolactam) grafted galactosylated chitosan (PNVCL-g-GC) was synthesized by EDC/NHS crosslinking. PNVCL-g-GC exhibited a temperature-dependent phase change (LCST) at 32?°C in aqueous solutions. PNVCL-g-GC hydrogel scaffold was fabricated by freeze-drying, and evaluated as a delivery vehicle dependent on environmental pH and temperature. PNVCL-g-GC was characterized using ATR-FTIR, 1H-NMR, DSC, TGA, rheometry, and SEM. The swelling degree increased by the decrease both in temperature and pH. A faster BSA release was observed at 40?°C and at pH 7.2 from the cytocompatible and hemocompatible copolymer.     

Synthesis and characteristics of interpenetrating polymer network hydrogel composed of chitosan and poly(acrylic acid)

Interpenetrating polymer network (IPN) hydrogels composed of chitosan and poly(acrylic acid) (PAAc) were synthesized by UV irradiation method, and their structure, crystallinity, swelling behavior, thermal property, and mechanical property were investigated. Chitosan/PAAc IPNs exhibited relatively high equilibrium water content and also showed reasonable sensitivity to pH. From the swelling behaviors at various pH's, Fourier transform infrared spectra at high temperature and thermal analysis confirmed the formation of polyelectrolyte complex due to the reaction between amino groups in chitosan and carboxyl groups in PAAc. For this reason, even at a swollen state, the present chitosan/PAAc IPNs possess good mechanical properties. Particularly, the CA‐2 sample (with a weight ratio of chitosan/PAAc = 50/50, molar ratio [NH₂]/[COOH] = 25/75) showed the lowest equilibrium water content and free water content, attributed to the more compact structure of the polyelectrolyte than CA‐1 or CA‐3 due to the high amount of interchain bond within the IPN. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 113–120, 1999     

Synthesis and characterization of in situ cross-linked hydrogel based on self-assembly of thiol-modified chitosan with PEG diacrylate using Michael type addition

A novel injectable in situ cross-linked hydrogel has been designed via Michael type addition between thiol-modified chitosan (CS-NAC) and PEG diacrylate (PEGDA). Hydrogel was rapidly formed in situ under physiological conditions. The gelation time depended on the content of free thiols in CS-NAC, temperature, and concentration of CS-NAC and PEGDA. Thermogravimetric analysis showed the thermal stabilities of hydrogels. SEM observation results confirmed a porous 3D structure. Rheological studies showed that the cross-linking density and elasticity of hydrogel had a correlation to the content of CS-NAC and PEGDA. Swelling studies revealed that these hydrogels had a high initial swelling and were degradable under physiological conditions. And swelling was highly temperature-dependent and was directly related to the amount of cross-linking. Biological activities of the hydrogels were evaluated by in vitro cell compatibility on HDFs and A549 cells and the results indicated that the hydrogel was biocompatible.     

Synthesis,characterization, and enzymatic degradation of chitosan/PEG hydrogel films

Poly(ethyleneglycol) (PEG)/tartaric acid (TA)‐crosslinked chitosan hydrogel (CPT) films were prepared, and the formation of the PEG/TA‐crosslinked structure was confirmed by Fourier transformed infrared (FTIR), nuclear magnetic resonance (NMR), and scanning electron microscope (SEM) measurements. The thermal properties of the crosslinked films were also determined with thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC) analysis. The swelling properties of the films were investigated at different temperature and pH values. It was found that the swelling ratio increased with the decrease of pH value of the surrounding buffer solutions, amount of PEG, and with the increase of temperature. Swelling behavior of the PEG/TA‐crosslinked chitosan hydrogel films depended on pH and reversible with the temperature. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis and characterization of photo-crosslinkable hydrogel membranes based on modified chitosan

In order to develop a non toxic and biocompatible hydrogel system with potential ability in biotechnology, modified photo-crosslinkable hydrogel membranes based on chitosan were prepared. Using an EDC/NHS conjugation method, chitosan was chemically modified to incorporate a photosensitive α-cyano-4-hydroxycinnamic acid moiety with various degrees of substitutions. Fourier transform infrared spectra (FTIR), proton nuclear magnetic resonance (¹H NMR) and ultraviolet-visible light spectra (UV-vis) were used for structural characterization of modified chitosan, The obtained membranes were crosslinked by irradiation in the ultraviolet region, where the photosensitive monomers showed maximum sensitivity. The prepared photo-crosslinked hydrogel membranes were investigated by thermal gravimetric analysis (TGA) and wide angle X-ray diffraction (WAXD). The swelling behaviors were investigated in terms of pH, time of swelling, and degree of substitution. Also, mechanical properties of the different photo-crosslinked hydrogel membranes were studied in both dry and wet conditions.     

Thermoreversible hydrogel. V. Synthesis and swelling behavior of the N-isopropylacrylamide-co-trimethyl methacryloyloxyethyl ammonium iodide copolymeric hydrogels

A series of N-isopropylacrylamide/trimethyl methacryloyloxyethyl ammonium iodide (NIPAAm/TMMAI) copolymeric gels are prepared from the various molar ratios of NIPAAm, cationic monomer TMMAI, and N,N′-methylene bisacrylamide (NMBA) in this article. The influences of the amount of the cationic monomer in the copolymeric gels on the swelling behavior in water, various saline solutions, and various temperatures are investigated. Results show that the swelling ratios of copolymeric gels are significantly larger than those of pure homopolymer NIPAAm gel, and the more the TMMAI content, the higher the gel transition temperature. In the saline solution, results show that the swelling ratio of pure NIPAAm gel has not significantly changed with an increase of the salt concentration until the salt concentration is larger than 0.1M. The swelling ratios for the copolymeric gels NIPAAm/TMMAI decrease with increasing salt concentration. In various saline solutions, results show that the anionic effects are greater than cationic effects in the presence of common anion, different cations and common cation, and different anions for these hydrogels. Finally, we also tested the reversibility of the NIPAAm/TMMAI copolymeric gels. The deswelling and reswelling kinetics are dependent on the temperature, which is below or above the gel transition temperature. The gel with little TMMAI content has a good reversibility. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 1793–1803, 1998     

一种光致变色水凝胶的合成与表征

合成了一种结合了螺吡喃(SP)的光致变色水凝胶,即N-乙烯基吡咯烷酮与N-异丙基丙烯酰胺共聚物水凝胶.红外光谱和溶胀实验的结果都表明,螺吡喃很好地结合进了水凝胶里.紫外-可见光谱的结果证明,合成的水凝胶具有光致变色特性,水凝胶对周期性交替的紫外光照射和黑暗条件的响应情况可以说明其光致变色的可回复性.从荧光显微镜照片可以...     

Synthesis and characterization of hydrophobically modified poly(vinyl alcohol) hydrogel membrane

Hydrophobically modified poly(vinyl alcohol), [PVA] was synthesized by graft copolymerization of N-tertiary butyl acrylamide [NTBA] onto PVA by free radical polymerization. The incorporation of NTBA onto PVA chains was confirmed by elemental analysis, FT-IR and NMR spectroscopy. A series of graft copolymers with different contents of NTBA were prepared and membranes were casted from these copolymer solutions in dimethyl sulfoxide. The increase in hydrophobicity with an increase in NTBA content was investigated by contact angle measurements. The swelling behaviour of membranes as a function of temperature, hydrophobic content, annealing temperature and period was studied. Permeability of solutes through these membranes was investigated as a function of solute size, membrane hydrophobicity and temperature. The swelling behaviour of the copolymer membranes showed that the lower content of NTBA gives discontinuous volume transition with respect to temperature whereas, the presence of higher amounts of NTBA showed decreased swelling ratios with very little influence of temperature on the swelling. The permeabilities of solutes through these membranes were strongly dependent on the size of the solute, solution temperature and hydrophobicity of the membrane. The copolymer membranes were further characterized using DSC, DMA and XRD. The peak becomes broader as the NTBA content increases.     

NVP接枝壳聚糖水凝胶的合成与溶胀性能

合成了N-乙烯基吡咯烷酮（NVP）接枝壳聚糖（CHI）水凝胶,讨论了NVP/CHI、引发剂、交联剂、聚合温度、乙酸浓度等因素对接枝率及凝胶溶胀性能的影响,NVP∶CHI为6时,接枝率达到300%以上. 溶胀温度、pH值、盐浓度等对凝胶溶胀性能的影响实验表明,凝胶表现出温度敏感性,在40 ℃出现最大平衡溶胀率,并观察到一级相转变;在中性或弱酸性介质中溶胀性能较好;与PVP凝胶相比,NVP接枝CHI凝胶表现出反聚电解质效应. 溶胀动力学研究表明,在溶胀前期,CHI含量较高时,凝胶趋向于非Fick溶胀,说明除了溶剂扩散外,凝胶网络链段弛豫、水分子与凝胶网络间及凝胶高分子链段间相互作用对凝胶溶胀性能的影响至关重要;CHI含量较高时则趋向于Fick溶胀.     

Synthesis and characterization of polyacrylamide‐grafted chitosan hydrogel microspheres for the controlled release of indomethacin

Microspheres of polyacrylamide‐grafted‐chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti‐inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug‐entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug‐release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non‐Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug‐diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non‐Fickian trend and the diffusion was relaxation‐controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003     

Synthesis and characterization of chitosan/poly(acrylic acid) polyelectrolyte complex

Polyelectrolyte complex based on chitosan and acrylic acid monomer by photoinitiated free‐radical polymerization in the absence of crosslinker showed a large transition in swelling in response to changes in pH of surrounding medium. Their ability to swell arises from polyelectrolyte interactions and molecular structure of the complex. The main properties of interest that related to the molecular structure, swelling volumes, glass transition temperature, and elastic modulus of the complex were investigated. The effect of water content, the only variable in the sample component, played an important role in molecular structure of the complex and as a consequence, the extent of intermolecular linkage, especially amide bonds which in turn governed the degree of swelling of the polyelectrolyte complex in this study. The decreased degree of swelling and higher temperature shift of glass transition temperature was found with increased water content, whereas increased modulus of elasticity of dry complex was found in lower water content of synthesis component. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1025–1035, 2002     

Preparation and characterization of chitosan/Cu(II) affinity membrane for urea adsorption

We used silica particles as a porogen to prepare macroporous chitosan membranes and subsequently prepared macroporous chitosan/Cu(II) affinity membranes for urea adsorption. The morphology, porosity, Cu(II) adsorption capacity, and swelling ratio of the macroporous membrane were measured. SEM photographs show the pores in the membrane dispersed uniformly, a feature that didn't change much after the adsorption of Cu(II). The porosity of the membrane had a maximum value when the silica/chitosan ratio was about 12. The Cu(II) adsorption capacity in the membrane leveled off when the initial concentration of CuSO₄ solution exceeded 5 × 10^?2 mol/L. The macroporous chitosan/Cu(II) affinity membrane was successfully used for urea adsorption. The maximum urea adsorption capacity was 78.8 mg/g membrane, which indicates that the membrane has a great potential for hemodialysis for urea removal. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1108–1112, 2003     

Preparation and characterization of glutaraldehyde crosslinked chitosan nanofiltration membrane

In this article, we prepare chitosan (CS) membrane on polyacrylonitrile (PAN) ultrafiltration membrane, and utilize the protonated amine group (? NH₃⁺) on the CS to retain γ‐aminobutyric acid (GABA) in a solution with a pH condition below the amino acid isoelectric point, so as to separate the amino acid from a mixture with sodium acetate that simulates the amino acid fermentation broth. To improve the acid resistance of the composite membrane, we chelate the amine groups on the CS by copper sulfate first, then crosslink the hydroxyl groups in glutaraldehyde solution, and remove the copper ion in hydrochloric acid finally to release the amine groups. This crosslinked CS/PAN composite membrane achieves 95% GABA rejection in pH 4.69 solution under the operation pressure of 0.2 MPa, while over 90% of the sodium acetate permeates the membrane. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and characterization of nanocomposite polyelectrolyte membranes based on Nafion ionomer and nanocrystalline hydroxyapatite

In this study nanocrystalline hydroxyapatite (nHA) was synthesized and characterized by means of FT-IR, XRD and TEM techniques and a series of proton exchange membranes based on Nafion^® and nHA were fabricated via solvent casting method. Thermogravimetric analysis confirmed thermal stability enhancement of the Nafion^® nanocomposite due to the presence of nHA nanopowder. SAXS and TEM analyses confirmed the incorporation of nHA into ionic phase of Nafion^®. Furthermore, the incorporation of elliptical nHA into the Nafion^® matrix improved proton conductivity of the resultant polyelectrolyte membrane up to 0.173 S cm⁻¹ at 2.0 wt% of nHA loading compared to that of 0.086 S cm⁻¹ for Nafion^® 117. Also, the inclusion of nHA nanoparticles into nanocomposite membranes resulted in a significant reduction of methanol permeability and crossover in comparison with pristine Nafion^® membranes. Membrane selectivity parameter of the nanocomposites at 2.0 wt% nHA was calculated and found to be 106,800 S s cm⁻³, which is more than two times than that of Nafion^® 117. Direct methanol fuel cell tests revealed that Nafion^®/nHA nanocomposite membranes were able to provide higher fuel cell efficiency and also better electrochemical performance in both low and high concentrations of methanol feed. Thus, the current study shows that nHA enhances the functionality of Nafion^® as fuel cell membranes.     

疏水型高强度水凝胶的合成与性能

以丙烯酰胺和疏水单体为原料 ,过硫酸钾 -硫酸亚铁为引发剂 ,采用溶液聚合法合成了疏水型高强度水凝胶。研究了单体组成、单体浓度、引发剂用量、交联剂用量、反应温度等因素对产物性能的影响。对比分析了疏水型水凝胶的吸水倍数、吸水速率和强度。疏水型水凝胶的强度大于常规高吸水性树脂 ,最长吸水时间长 ,吸水速度平缓。对疏水型高强度水凝胶强度进行了统计回归分析 ,对吸水速率和最长吸水时间进行了分析描述。     

硅水凝胶隐形眼镜材料的合成与性能研究

以甲基丙烯酸羟乙酯（HEMA）、N-乙烯基毗咯烷酮（NVP）和γ-（甲基丙烯酰氧）丙基三甲氧基硅烷（KH-570）为单体,以偶氮二异丁腈（AIBN）为引发剂,通过本体聚合反应合成新型硅水凝胶角膜接触镜.考察了各单体配比、反应温度等对聚合的影响.结果表明,当反应温度为90℃,反应时间为2h,V（HEMA）：V（NVP）：V（KH-570） =8∶ 1∶1时,合成的隐形眼镜透氧量（DK/t）达到64.0×10-9（cm3O2·cm）/（cm2·s·mmHg）,含水量38％,透光率95.5％以上.     

Sorption and desorption of water vapour by membranes of the polyelectrolyte complex of chitosan and carboxymethyl cellulose

Sorption of water vapour by chitosan/carboxymethyl cellulose polyelectrolyte complex membranes prepared at two different pHs was studied. A linear dependence of the water uptake (W) on time was observed for W values lower than 0.5 g of water per gram of membrane. For higher values of W diffusion becomes controlled by the relaxation of the chains, and second-order kinetics is observed. An equation that satisfactorily reproduces this behaviour is proposed. Desorption experiments were carried out at different temperatures and the W versus time curves obtained exhibited the same general pattern and were also adjusted by this equation. The approximate average diffusion coefficients were evaluated at each temperature and the apparent activation energy for the diffusion process is reported.     

Synthesis and characterization of a novel pH-responsive nanocomposite hydrogel based on chitosan for targeted drug release

Over the last decade, nanocomposite hydrogels have been provided a new approach for the biomedical field. In this work, a novel pH-responsive nanocomposite hydrogel was fabricated using simultaneous in situ formation of magnetite iron oxide nanoparticles and hydrogel networks of poly(acrylic acid) grafted onto chitosan. The effects of various types of precursor molecules, pH, salt, and loading pressure were examined on the swelling properties of resulting nanocomposite hydrogels. The synthesized nanocomposite hydrogel was well characterized using different instruments. In vitro drug releasing behavior of doxorubicin was studied at pH 5.4 and 7.4. The drug release mechanism was investigated through different kinetic models. These experimental results open a new opportunity to make pH-responsive nanocomposite hydrogel devices for controlled delivery of drug.     

Humic acid embedded chitosan/poly (vinyl alcohol) pH-sensitive hydrogel: Synthesis,characterization, swelling kinetic and diffusion coefficient

In the present research, humic acid (HA) embedded chitosan (CHT)-poly (vinyl alcohol) (PVA) pH-sensitive hydrogels have been synthesized using glutaraldehyde as a crosslinker. The hydrogels were characterized by Fourier-transform infrared (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis. The effect of HA content, pH, and temperature on the equilibrium solvent uptake has been investigated. With higher HA contents, the equilibrium swelling capacity increases while lower concentrations of acid cause a decrease in the degree of the swelling. The hydrogels have been found to undergo a number of swelling/deswelling cycles when pH of the swelling medium changes from 1.5 to 11.0. Fick’s law, first-order, and second-order kinetic models were applied to the swelling ratio of hydrogels to explain the mass transfer mechanism and specify swelling kinetic parameters. The swelling parameters such as equilibrium swelling capacity, swelling rate constant, swelling exponent, initial swelling rate, diffusion coefficient, etc., have been evaluated.     

Thermosensitive chitosan hydrogel for implantable drug delivery: Blending PVA to mitigate body response and promote bioavailability

Thermosensitive hydrogels promise to be the injectable implants for long-term controlled drug release; however, body response to the implanted hydrogels and its unpredictable impacts on drug release complicates their applications. In the present study, hydrophilic polymer poly(vinyl alcohol) (PVA) was blended into the thermosensitive hydrogel composed of chitosan and glycerophosphate to mitigate the body responses and promote the drug bioavailability. The effects of PVA on the surface properties of the hydrogel were evaluated by zeta-potential, water contact angle, and cell attachment. Body responses were explored by histological examination via subcutaneously implanting the hydrogels into Sprague-Dawley rats. Drug release in vivo and bioavailability were determined with cyclosporine A (CsA) employed as the model drug. The results showed that, on one hand, the presence of PVA improved the surface hydrophilicity of the hydrogel and inhibited the cell attachment on the hydrogel, which alleviated the further cell infiltration and tissue integration in body; and on the other hand, blending of PVA led to the more rapid gel formation and more compact network, which resisted the dehydration and survived the hydrogel from cell division. These advantages benefited the controlled release and absorption of CsA, and contributed to the higher drug bioavailability. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012