Crosslinked Networks Based on Polysaccharides and Collagen for Pilocarpine Sustained Release

The paper presents the experimental studies regarding synthesis and characterization of hydrogels based on gellan (Gel)/chitosan (CS) and collagen (Col), obtained by crosslinking with glutaraldehyde (GLA). The influence of the polysaccharide content and GLA ratio on the final composition and swelling characteristics was evaluated. Hydrogels swelling analysis, in distilled water and phosphate buffer (PBS, pH 7.2) has shown higher swelling degrees at increased concentration of polysaccharide into hydrogels. In vitro release of pilocarpine has demonstrated the possibility to use gellan-collagen and chitosan-collagen hydrogels as ophthalmic drug delivery matrix.     

Metal adsorption of carboxymethyl cellulose/carboxymethyl chitosan blend hydrogels prepared by Gamma irradiation

Blend hydrogels based on the carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCts) were prepared by γ-irradiation of a high concentrated CMC/CMCts aqueous solution. Properties of the hydrogels, such as gel fraction, swelling ratio, gel strength, and metal adsorption for Pb and Au were investigated. The gel fraction increased with increasing dose, while the swelling ratio decreased with increasing it. The obtained blend hydrogels had high adsorption performance which was controlled by adjusting the composition of CMC/CMCts.     

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 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.      

Swelling behavior of chitosan hydrogels in ionic liquid-water binary systems

The swelling behavior of chitosan hydrogels in ionic liquid-water binary systems was studied using hydrophilic room-temperature ionic liquids (RTILs) to elucidate the swelling mechanism of chitosan hydrogels. No penetration of RTIL into a dry chitosan material was observed. Swelling was achieved by soaking in water-RTIL binary mixtures, with larger swelling observed at higher water contents. In one instance, the binary mixture was acidic and produced larger than expected swelling due to the dissociation of the amine groups in the chitosan. The equilibrium binary system content behavior of the chitosan hydrogels depended upon the amount of free water, which is a measure of the number of water molecules that do not interact with the ionic liquid. After evaporation of water, remnant RTIL remained in the chitosan network and hardness testing indicated a plasticization effect, suggesting that the RTIL molecularly mixed with the chitosan. Chitosan hydrogels containing only RTIL were prepared by dropping pure RTIL onto a fully preswollen hydrogel followed by water evaporation. This method may be a useful means for preparing air-stable swollen chitosan gels.     

Physical Hydrogels of Poly(vinyl alcohol) with Different Syndiotacticity Prepared in the Presence of Lactosilated Chitosan Derivatives

Poly(vinyl alcohol) (PVA) physical hydrogels were prepared by repeated freeze–thawing cycles using aqueous solutions of two PVA samples having different degrees of syndiotacticity, a‐PVA and s‐PVA with 55% and 61% of syndiotactic diads, respectively. The hydrogels were prepared in the presence of different amounts of lactosilated chitosan derivatives (LC) of different molecular weight. The PVA stereoregularity was found to have a dramatic effect on the amount of PVA incorporated into the hydrogels, leading to remarkable differences in the swelling degree and porosity of a‐PVA and s‐PVA hydrogels. A significant amount of LC was retained in the hydrogels after equilibrium swelling. The swelling of the a‐PVA hydrogels was found to increase significantly by increasing the amount of LC while it was only slightly increased in the case of s‐PVA hydrogels. The amount of LC released after equilibrium swelling was lower when chitosan derivatives with higher molecular weights were used. Increased initial concentrations of LC resulted in much higher porosity of the hydrogels. TGA and DSC studies showed that LC is stabilized by the incorporation in the PVA hydrogels. The melting temperature of the crystalline regions of PVA was not significantly influenced by LC. Conversely, the extension of the crystalline domains increased in the presence of LC. The retention of a chitosan derivative bearing β‐D ‐galactose side chain residues makes these hydrogels potentially useful as scaffolds for hepatocytes culture.

Scanning electron micrographs of PVA‐LC hydrogels: (a) a‐PVA; (b) a‐PVA/LC₁₅₀ 80:20; (c) a‐PVA/LC₁₅₀ 50:50.     

Studies on syntheses and dynamic swelling of pH-sensitive macroporous poly(N-isopropylacrylamide-co-acrylic acid) hydrogels

A series of macroporous poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAm-AA) hydrogels with different composition were synthesized by free-radical copolymerization in the presence of silica particles as a pore generating agent. The equilibrium swelling ratio, half swelling time and dynamic swelling kinetics of the copolymers previously soaked in different acidic buffer solutions were investigated at pH 7 at 25°C. Experimental results revealed that the swelling rate of the macroporous hydrogels was greatly increased compared to conventional hydrogels due to existence of the macroporous structures. It was found that the swelling history of previously putting in acidic solutions copolymers had strong influence on their dynamic swelling kinetics especially for the samples ranging in composition between 30 and 70 mol % of NIPAAm, whereas the swelling history had little influence on the equilibrium swelling ratio of copolymers. The swelling pattern exhibits sigmoid swelling curves. This is explained by an autocatalytic mechanism. The hydrogen bonding dissociation plays an important role in the dynamic swelling behavior.     

Swelling Kinetics of Interpenetrating Polymer Hydrogels Composed of Poly(Vinyl Alcohol)/Chitosan

Interpenetrating polymer network (IPN) hydrogels based on poly(vinyl alcohol)/chitosan were prepared by UV irradiation. The swelling behavior of the IPN hydrogels was studied by immersion of the films in deionized water at various temperatures and in buffer solutions at various pHs. IPN3 exhibited a relatively high swelling ratio. The swelling ratio increased with an increase in the content of chitosan and were higher in acidic rather than in alkaline pHs. The overall swelling process was anomalous diffusion due to polymer relaxation. The diffusion coefficient values increased with an increase in temperature and the content of chitosan.     

Synthesis and characterization of novel carboxymethyl chitosan grafted polylactide hydrogels for controlled drug delivery

Novel carboxymethyl chitosan‐polylactide (CMCS‐g‐PLA) hydrogels were prepared by using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride/N‐hydroxysuccinimide (EDC/NHS) as crosslinking agent and catalyst at room temperature. Solid‐state ¹³C‐NMR, SEM, and FT‐IR measurements showed that PLA blocks are successfully grafted onto the CMCS main chains. DSC measurements confirmed the effective crosslinking of carboxymethyl chitosan. With increasing the amount of EDC/NHS, the crosslink destiny of CMCS‐g‐PLA copolymers is improved. The swelling ratio of CMCS‐g‐PLA hydrogels is pH dependent, showing a minimum in the pH range of 3 to 5. Rheological studies confirmed the formation of hydrogels. The higher the crosslinking density, the higher the storage modulus of hydrogels. CMCS‐g‐PLA hydrogels only slightly degrade in PBS for 10 days. In the presence of lysozyme, however, hydrogels with low crosslink density are totally degraded in 10 days. Drug release studies show that after 96 h, 95% of thymopentin is released under in vitro conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Swelling Behavior of Semi‐Interpenetrating Polymer Network Hydrogels Based on Chitosan and Poly(acryl amide)

Semi‐interpenetrating polymer networks (semi‐IPNs) composed of chitosan and polyacrylamide (PAAm) hydrogels have been prepared, and the effect of changing pH, temperature, ionic concentration, and applied electric fields on the swelling of the hydrogels was investigated. The swelling kinetics increased rapidly, reaching equilibrium within 60 min. The semi‐IPN hydrogels exhibited a relatively high swelling ratios of 385%–569% at T=25°C. The swelling ratio increased with decreasing pH below pH=7 due to the dissociation of ionic bonds. The swelling ratio of the semi‐IPN hydrogels was pH, ionic concentration, temperature, and electric field dependent. Differential scanning calorimetry (DSC) was used to determine the volume of free water in the semi‐IPN hydrogels, which was found to increase with increasing PAAm content.     

羧甲基纤维素与丙烯酸接枝共聚凝胶的溶胀动力学及过溶胀平衡特性的研究

采用接枝共聚合成了羧甲基纤维素钠、丙烯酸与N,N′-亚甲基双丙烯酰胺的交联凝胶, 研究了这类凝胶在不同pH值的缓冲溶液中的溶胀行为, 发现在酸性介质中凝胶的溶胀动力学行为表现出过溶胀平衡特性(overshooting effect), 即凝胶先发生溶胀到最大值, 然后再逐渐消溶胀到平衡. 这种现象可归因于凝胶溶胀过程中羧基之间通过氢键所产生的协同物理交联. 较之凝胶的组成, 缓冲溶液的pH值对过溶胀平衡现象的影响更为显著. 前者是因为凝胶羧基的总摩尔分数并不随两组分结构单元摩尔数的改变而改变, 羧基之间通过氢键形成的物理交联程度在交联剂摩尔分数接近的条件下变化不大; 后者是由于溶液的pH值显著影响凝胶羧基的质子化程度, 进而影响羧基之间通过氢键形成的物理交联程度. 凝胶在酸性介质中的溶胀过程符合E. Díez-Peña等提出的溶胀动力学定量模型, 理论曲线与实验数据有较好的相关性. 凝胶在pH≥5.0的缓冲溶液中的溶胀不产生过溶胀平衡现象, 这一现象归因于完全离子化的羧基之间不能形成物理交联. 凝胶的溶胀过程遵循Schott二级溶胀动力学.     

Modified chitosan III,superabsorbency, salt‐ and pH‐sensitivity of smart ampholytic hydrogels from chitosan‐g‐PAN

Polyacrylonitrile (PAN) grafted chitosan was prepared by ceric‐initiated graft polymerization of acrylonitrile onto chitosan in a homogenous medium. The copolymer chitosan‐g‐PAN product was then hydrolyzed to yield a novel smart hydrogel (H‐chitoPAN) with superabsorbing properties. The influence of add‐on values as well as temperature and time of hydrolysis of the initial chitosan‐g‐PAN on swelling behavior of the hydrogel was evaluated in water and various salt solutions. The swelling kinetics of the superabsorbing hydrogel was studied as well. The hydrogels exhibited ampholytic and pH‐sensitivity characteristics. Several sharp swelling changes were observed in lieu of pH variations in a wide range (pH 2–13). The swelling variations were explained according to swelling theory based on the hydrogel chemical structure. Superabsorbency, pH‐ and salt‐sensitivity of the chitosan‐based hydrogel was briefly compared with the classical starch‐based superabsorbent, H‐SPAN. The pH‐reversibility and on–off switching behavior of the intelligent H‐chitoPAN hydrogels makes them good candidates for considering as potential drug carries. Copyright © 2004 John Wiley & Sons, Ltd.     

两亲型羧甲基壳聚糖衍生物的合成及体外药物释放

通过羧甲基壳聚糖与醛和乳糖反应制得N-烷基乳糖基-O,N-羧甲基壳聚糖,并以戊二醛为交联剂制成水凝胶;以人血清蛋白作为模型药物,初步探讨了该水凝胶对蛋白类药物的释放规律。结果表明:该水凝胶具有亲水-疏水两亲性和不同于壳聚糖的pH敏感性,有望应用于蛋白类药物的控制释放。     

Investigation of the swelling behavior of hydrogels derived from high-molecular-weight poly(2-ethyl-2-oxazoline)

Thermoresponsive hydrogels are of great importance as smart materials. They are usually composed of cross-linked polymers with a lower critical solution temperature (LCST). Although much is known about networks of poly(N-isopropylacrylamide), all other polymers are somewhat neglected. In this work, the temperature-dependent swelling behavior of differently cross-linked thermoresponsive poly(2-ethyl-2-oxazoline) (PEtOx) hydrogels were investigated with regard to varying parameters of the network composition. It was found that the degrees of swelling of the hydrogels converge for a certain polymer/solvent system at a distinct temperature independent of its degree of cross-linking. Furthermore, this temperature correlates with the LCST of the respective starting PEtOx. Its net chain molecular weight M_c only affects the maximum degree of swelling and thus, the swelling–deswelling rate of the hydrogel. The fundamental structure/property relations found in this study could be useful to predict the behavior of other thermoresponsive hydrogels.     

Swelling Kinetics of Microgels Embedded in a Polyacrylamide Hydrogel Matrix

Composite hydrogels—macroscopic hydrogels with embedded microgel particles—are expected to respond to external stimuli quickly because microgels swell much faster than bulky gels. In this work, the kinetics of the pH‐induced swelling of a composite hydrogel are studied using turbidity measurements. The embedded microgel is a pH‐ and thermosensitive poly(N‐isopropylacrylamide‐co‐acrylic acid) microgel and the hydrogel matrix is polyacrylamide. A rapid pH‐induced swelling of the embedded microgel particles is observed, confirming that composite hydrogels respond faster than ordinary hydrogels. However, compared with the free microgels, the swelling of the embedded microgel is much slower. Diffusion of OH^? into the composite hydrogel film is identified as the main reason for the slow swelling of the embedded microgel particles, as the time of the pH‐induced swelling of this film is comparable to that of OH^? diffusion into the film. The composition of the hydrogel matrix does not significantly change the characteristic swelling time of the composite hydrogel film. However, the swelling pattern of the film changes with composition of the hydrogel matrix.     

A novel polyacrylamide nanocomposite hydrogel reinforced with natural chitosan nanofibers

Polyacrylamide (PAM) was used as a matrix material for fabricating novel nanocomposite hydrogels reinforced with natural chitosan nanofibers (CNFs) via in situ free-radical polymerization. The nanocomposite's structure, strength, morphology and rheological properties were investigated. The results showed that the CNFs had a strong interaction with PAM through hydrogen and covalent bondings. The CNFs acted as a multifunctional cross-linker and a reinforcing agent in the hydrogel system. The compression strength and storage modulus of the nanocomposite hydrogels were significantly higher than those of the pure PAM hydrogels and the corresponding PAM/chitosan semi-interpenetrating polymer network (PAM-SIPN) hydrogels. The swelling ratio (SR) of the nanocomposite hydrogels was lower than that of the PAM hydrogel, but was similar to that of the PAM-SIPN hydrogel. Among the CNF contents used, the 1.5 wt% CNF loading level showed the best combined swelling and mechanical properties for the hydrogels.     

Synthesis and characterization of antibacterial semi-interpenetrating carboxymethyl chitosan/poly (acrylonitrile) hydrogels

Blend hydrogels composed of carboxymethyl chitosan (CMCh) and poly (acrylonitrile) (PAN) were synthesized via crosslinking method. Several analyses were made to investigate both physical and thermal properties of CMCh/PAN hydrogels like; FTIR, scanning electron microscope, XRD and thermogravimetric analysis (TGA). TGA results showed that CMCh/PAN hydrogels are thermally more stable than CMCh and their thermal stability increases as PAN content increases in the hydrogel. Moreover, the swelling behavior of CMCh/PAN hydrogels was studied in different buffer solutions. It was found that CMCh/PAN hydrogels swell much more than PAN especially at pH 9. The hydrogels sorption for different dyestuff and various metal ions like; Cu²⁺, Cd²⁺ and Co²⁺ were also studied. In this work, antibacterial characteristic of hydrogels was mainly investigated towards Escherichia coli (E. coli) as a serious disease-leading bacterium. All tested hydrogels have clearly presented good antibacterial activity as CMCh content increases in the hydrogels.     

Chitosan-Carboxymethylcellulose Hydrogels as Supports for cell Immobilization

Abstract

The preparation of hydrogels from the polyelectrolyte complexation (PEC) of carboxymethylcellulose (CMC) and hydrogels from the complexation with an additional or simultaneous ionotropic gelation is reported. The reaction yield is high enough and depends strongly on the additional ionotropic gelation (IG). Infrared spectroscopy was used to confirm complexation between the carboxylic (in CMC) and amine (in chitosan) groups. The scanning electron microscope images show the formation of a fibrillar structure with characteristic pore sizes between 0.1 and 1 μm. The swelling capacity, Q, of PEC hydrogels is not high, but the Q value of hydrogels from PEC with an additional IG is high and depends strongly on the pH medium. These hydrogels are mechanically more stable than the PEC hydrogels; their mechanical strength is about 7 times higher than that of PEC hydrogels. The hydrogels were used to immobilize yeast cells with the cell density 1 × 10⁹ cells/mL, about 100 times higher than that in the free-cell culture. Only the hydrogels with additional IG were stable enough for continuous fermentation over 10 days. These hydrogels proved to have higher affinity to substrate, which led to higher productivity than the ionotropic gel of CMC and aluminum ion.     

Swelling behavior of amphiphilic hydrogels of copolymers of the vinyl ether of ethylene glycol and vinyl isobutyl ether,and their interaction with cationic surfactant

Amphiphilic hydrogels of copolymers of the vinyl ether of ethylene glycol and vinyl isobutyl ether were synthesized by -radiation-induced free radical polymerization. Hydrogels with certain copolymer compositions showed thermo-sensitive behavior in aqueous solutions. The swelling behavior of the hydrogels in cetylpyridinium bromide aqueous solution was studied. Increased swelling of the hydrogels was observed in the surfactant solutions. The increased swelling was more prominent for the hydrogels with a higher content of hydrophobic moiety in the copolymer composition, and with higher surfactant concentration. The reason for this phenomenon is discussed. Treatment of some hydrogels in the surfactant solutions resulted in higher swelling ability in distilled water with distinct thermo-induced contraction over a narrow temperature interval.     

Dual thermo‐ and pH‐sensitive network‐grafted hydrogels formed by macrocrosslinker as drug delivery system

Dual thermo‐ and pH‐sensitive network‐grafted hydrogels made of poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) network and poly(N‐isopropylacrylamide) (PNIPAM) grafting chains were successfully synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition‐fragmentation chain transfer (RAFT) polymerization, and click chemistry. PNIPAM having two azide groups at one chain end [PNIPAM‐(N₃)₂] was prepared with an azide‐capped ATRP initiator of N,N‐di(β‐azidoethyl) 2‐chloropropionylamide. Alkyne‐pending poly(N,N‐dimethylaminoethyl methacrylate‐co‐propargyl acrylate) [P(DMAEMA‐co‐ProA)] was obtained through RAFT copolymerization using dibenzyltrithiocarbonate as chain transfer agent. The subsequent click reaction led to the formation of the network‐grafted hydrogels. The influences of the chemical composition of P(DMAEMA‐co‐ProA) on the properties of the hydrogels were investigated in terms of morphology and swelling/deswelling kinetics. The dual stimulus‐sensitive hydrogels exhibited fast response, high swelling ratio, and reproducible swelling/deswelling cycles under different temperatures and pH values. The uptake and release of ceftriaxone sodium by these hydrogels showed both thermal and pH dependence, suggesting the feasibility of these hydrogels as thermo‐ and pH‐dependent drug release devices. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011