Polyelectrolyte Complex Hydrogel Research Articles

Gelatin–κ-carrageenan polyelectrolyte complex hydrogel compositions for the design and development of extended-release pellets

ABSTRACTPresent investigation was aimed to develop Zaltoprofen-loaded extended-release (ER) pellets formulation for prolonged release. The matrix type of pellets was prepared by extrusion-spheronization technique using calcium chloride-mediated gelatin–κ-carrageenan (G–κ-Carr) polyelectrolyte complex (PEC) hydrogel using rotatable central composite design. The pellets were characterized for physicochemical, morphological, solid-state characterization and flow properties. The formulations were also estimated for drug release and mucoadhesion potential. The optimized formulation (F1) containing 5:5 ratio of G–κ-Carr showed a drug release up to 98.2% and mucoadhesion of 95%. Optimized formulation showed acceptable release pattern, and hence would be viable alternative to ER type of formulations.

Dually pH-responsive polyelectrolyte complex hydrogel composed of polyacrylic acid and poly (2-(dimthylamino) ethyl methacrylate)

Via the radical polymerization of 2-(dimthylamino) ethyl methacrylate in the polyacrylic acid solution, we obtain the dually pH-reponsive polyelectrolytes complex hydrogel, which could be triggered to be swollen either in acid and basic environments. The results show that the responsive behavior of these PEC hydrogels is insensitive to monomer concentration in the prepolymerization, but can be tuned by changing the charge ratio or introducing chemical crosslinker. Moreover, other amazing propertise of the prepared PEC hydrogel are presented, which are including the ionic strength-responsiveness, the modest mechanical property (a tensile stress of 0.2 MPa and a tensile strain of 1500%) and the self-healing ability (a self-healing efficiency of ca. 70%). In brief, we report a multi-functional hydrogel which might serve as a new platform for responsive materials.

Integrated three‐dimensional fiber/hydrogel biphasic scaffolds for periodontal bone tissue engineering

AbstractCombining a tissue engineering scaffold made of a load‐bearing polymer with a hydrogel represents a powerful approach to enhancing the functionalities of the resulting biphasic construct, such as its mechanical properties or ability to support cellular colonization. This research activity was aimed at the development of biphasic scaffolds through the combination of an additively manufactured poly(ϵ‐caprolactone) (PCL) fiber construct and a chitosan/poly(γ‐glutamic acid) polyelectrolyte complex hydrogel. By investigating a set of layered structures made of PCL or PCL/hydroxyapatite composite, biphasic scaffold prototypes with good integration of the two phases at the macroscale and microscale were developed. The biphasic constructs were able to absorb cell culture medium up to 10‐fold of their weight, and the combination of the two phases had a significant influence on compressive mechanical properties compared with hydrogel or PCL scaffold alone. In addition, due to the presence of chitosan in the hydrogel phase, biphasic scaffolds exerted a broad‐spectrum antibacterial activity. The developed biphasic systems appear well suited for application in periodontal bone regenerative approaches in which a biodegradable porous structure providing mechanical stability and a hydrogel phase functioning as absorbing depot of endogenous proteins are simultaneously required. © 2016 Society of Chemical Industry

Modelling of pancreatic ductal adenocarcinoma in vitro with three-dimensional microstructured hydrogels

Development of a novelin vitro3D model of pancreas cancer based on microstructured polyelectrolyte complex (mPEC) hydrogel.

Preparation and cytotoxicity of N,N,N-trimethyl chitosan/alginate beads containing gold nanoparticles

Polyelectrolyte complex beads based on N,N,N-trimethyl chitosan (TMC) and sodium alginate (ALG) were obtained. This biomaterial was characterised by FTIR, TGA/DTG, DSC and SEM analysis. The good properties of polyelectrolyte complex hydrogel beads were associated, for the first time, with gold nanoparticles (AuNPs). Through a straightforward methodology, AuNPs were encapsulated into the beads. The in vitro cytotoxicity assays on the Caco-2 colon cancer cells and healthy VERO cells showed that the beads presented good biocompatibility on both cell lines, whereas the beads loaded with gold nanoparticles (beads/AuNPs) was slightly cytotoxic on the Caco-2 and VERO cells.

A Novel Chitosan-γPGA Polyelectrolyte Complex Hydrogel Promotes Early New Bone Formation in the Alveolar Socket Following Tooth Extraction

A novel chitosan-γPGA polyelectrolyte complex hydrogel (C-PGA) has been developed and proven to be an effective dressing for wound healing. The purpose of this study was to evaluate if C-PGA could promote new bone formation in the alveolar socket following tooth extraction. An animal model was proposed using radiography and histomorphology simultaneously to analyze the symmetrical sections of Wistar rats. The upper incisors of Wistar rats were extracted and the extraction sockets were randomly treated with gelatin sponge, neat chitosan, C-PGA, or received no treatment. The extraction sockets of selected rats from each group were evaluated at 1, 2, 4, or 6 wk post-extraction. The results of radiography and histopathology indicated that the extraction sockets treated with C-PGA exhibited lamellar bone formation (6.5%) as early as 2 wk after the extraction was performed. Moreover, the degree of new bone formation was significantly higher (P < 0.05) in the extraction sockets treated with C-PGA at 6 wk post-extraction than that in the other study groups. In this study, we demonstrated that the proposed animal model involving symmetrical sections and simultaneous radiography and histomorphology evaluation is feasible. We also conclude that the novel C-PGA has great potential for new bone formation in the alveolar socket following tooth extraction.

IMMOBILIZATION OF CARBONIC ANHYDRASE ENZYME PURIFIED FROM Bacillus subtilis VSG-4 AND ITS APPLICATION AS CO2 SEQUESTERER

The purification, immobilization, and characterization of carbonic anhydrase (CA) secreted by Bacillus subtilis VSG-4 isolated from tropical soil have been investigated in this work. Carbonic anhydrase was purified using ammonium sulfate precipitation, Sephadex-G-75 column chromatography, and DEAE-cellulose chromatography, achieving a 24.6-fold purification. The apparent molecular mass of purified CA obtained by SDS-PAGE was found to be 37 kD. The purified CA was entrapped within a chitosan–alginate polyelectrolyte complex (C-A PEC) hydrogel for potential use as an immobilized enzyme. The optimum pH and temperature for both free and immobilized enzymes were 8.2 and 37°C, respectively. The immobilized enzyme had a much higher storage stability than the free enzyme. Certain metal ions, namely, Co2+, Cu2+, and Fe3+, increased the enzyme activity, whereas CA activity was inhibited by Pb2+, Hg2+, ethylenediamine tetraacetic acid (EDTA), 5,5′-dithiobis-(2-nitrobenzoic acid (DTNB), and acetazolamide. Free and immobilized CAs were tested further for the targeted application of the carbonation reaction to convert CO2 to CaCO3. The maximum CO2 sequestration potential was achieved with immobilized CA (480 mg CaCO3/mg protein). These properties suggest that immobilized VSG-4 carbonic anhydrase has the potential to be used for biomimetic CO2 sequestration.

A novel injectable chitosan/polyglutamate polyelectrolyte complex hydrogel with hydroxyapatite for soft-tissue augmentation

This study demonstrated a chitosan (CS)/polyglutamate (PG) polyelectrolyte complex (PEC) hydrogel combined with spherical hydroxyapatite (HAp) particles as an injectable dermal filler for soft-tissue augmentation. The CS/PG PEC hydrogel with oppositely charged ionic cross-linking, a high gel content, and low degradation rate was introduced as a carrier to achieve high shape and volume stability. An MTT assay indicated that the CS/PG PEC had satisfactory cell biocompatibility. This PEC/HAp hydrogel showed good structural integrity in a PBS solution for up to 60 days. Clinical manageability was indexed by an injection force measurement through sterile 27-gauge needles using a texture analyzer. In an animal study, 0.2mL of the PEC and PEC/hydroxyapatite (HAp) were implanted within the dorsal dermis of a swine ear. Injected tissue areas were biopsied 2 weeks, and 2 and 6 months after the injection. According to the histomorphometric results, the PEC and PEC/HAp groups showed percentages of retention of the maximum height of the cross-section of about 44% and 73% at 6 months. New collagen was observed in the central position indicating a possible collagenesis effect. These results suggest that this PEC/HAp system can be used as an alternative for soft-tissue augmentation.

Antibacterial activity and biocompatibility of a chitosan–γ-poly(glutamic acid) polyelectrolyte complex hydrogel

In this study, we prepared a polyelectrolyte complex (PEC) hydrogel comprising chitosan as the cationic polyelectrolyte and γ-poly(glutamic acid) (γ-PGA) as the anionic polyelectrolyte. Fourier transform infrared spectroscopy revealed that ionic complex interactions existed in the chitosan–γ-PGA PEC hydrogels. The compressive modulus increased upon increasing the degree of complex formation in the chitosan–γ-PGA PEC hydrogel; the water uptake decreased upon increasing the degree of complex formation. At the same degree of complex formation, the compressive modulus was larger for the chitosan-dominated PEC hydrogels; the water uptake was larger for the γ-PGA-dominated ones. Scanning electron microscopy images revealed the existence of interconnected porous structures (pore size: 30–100 μm) in all of the chitosan–γ-PGA PEC hydrogels. The chitosan–γ-PGA PEC hydrogels also exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, in vitro cell culturing of 3T3 fibroblasts revealed that all the chitosan–γ-PGA PEC hydrogels were effective in promoting cell proliferation, especially the positively charged ones (chitosan-dominated). Therefore, the chitosan–γ-PGA polyelectrolyte hydrogel appears to have potential as a new material for biomedical applications.

The studies on the stimuli‐response of poly (N,N‐dimethylamino ethyl methacrylate/acrylic acid‐co‐acrylamide) complex hydrogel under DC electric field

AbstractA polyelectrolyte complex hydrogel, poly (N,N‐dimethylaminoethyl methacrylate/acrylic acid‐co‐acrylamide) hydrogel designed as PDMEAA, was prepared by the free radical copolymerization in aqueous solutions. Without chemical crosslinker, PDMEAA hydrogel network was formed by electrostatic attraction of the proton‐transfer between acrylic acid and N,N‐dimethylamino ethyl methacrylate. Since the electrostatic attraction could be weakened by the application of electric field, PDMEAA hydrogel was decomposed under contacted electric field. Various factors such as gel composition, the species and concentration of electrolytes, voltage, and the experimental set‐ups, could effect the decomposing process of PDMEAA hydrogel. In CaCl2 and MgCl2 solutions, PDMEAA hydrogel had no change under electric field. And in high concentration of NaCl and Na2SO4 solutions, PDMEAA hydrogel has been eroded linearly with the increasing time applied electric field. In low concentration of NaCl and Na2SO4 solutions, however, a swelling process was found before the erosion. The stimuli‐responsive mechanism was investigated through scanning electron microscope (SEM) and gel permeation chromatography (GPC). © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

A Novel Polyelectrolyte Complex (PEC) Hydrogel for Controlled Drug Delivery to the Distal Intestine

This work was aimed at preparing and evaluating a physically crosslinked hydrogel for the controlled release of diverse drugs to the distal intestine. A solution of fluorescein isothiocyanate dextran, MW 4400 Da (FD4), or a dispersion of micronized dexamethasone (DMS) was microencapsulated into a PEC hydrogel, composed of polycationic N-trimethyl chitosan (TMC) and polyanionic N-carboxymethyl chitosan (CMCh). A fine spray of a 1% CMCh solution containing 1% FD4 in solution or 0.1% DMS in dispersion was directed into a 2% TMC solution, then the resulting microcapsules (MCPS) were lyophilized. MCPS were analyzed by SEM and solid-state NMR. Drug release from MCPS was too fast, so these were compressed into matrices (weight 20 mg; diameter 6 mm; drug load 2.5%, with FD4, or 3.7%, with DMS) which were enteric coated. Drug release from matrices was studied simulating matrix transit across GI environments of different pHs, from stomach to proximal colon. The enteric film hindered release in stomach and proximal small intestine. After film dissolution at ileum pH, release occurred with a pattern described by the Peppas equation (n=0.6, with DMS; n=0.7, with FD4). As the pH changed from 7.4 to 6 (from ileum to ascending colon) MCPS were liberated from matrix surface. This phenomenon sustained the release rate. The present MCPS allow controlled doses of macromolecular or mi- croparticulate drugs being uniformly loaded into controlled-release matrices based on a physically crosslinked, biodegrad- able hydrogel.

Preparation and evaluation of chitosan/carrageenan beads for controlled release of sodium diclofenac

The polyelectrolyte complex (PEC) hydrogel beads based on chitosan (CS) and carrageenan (CR) have been studied as a controlled release device to deliver sodium diclofenac (DFNa) in the simulated gastrointestinal condition. Various factors potentially influencing the drug release (ie, CS/CR proportion, DFNa content, types and amount of cross-linking agents) were also investigated. The optimal formulation was obtained with CS/CR proportion of 2/1 and 5% (wt/vol) DFNa. The controlled release of the drug from this formulation was superior to other formulations and was able to maintain the release for approximately 8 hours. Upon cross-linking with glutaric acid and glutaraldehyde, the resulting beads were found to be more efficient for prolonged drug release than their non-cross-linking counterparts. The bead cross-linked with glutaraldehyde was able to control the release of the drug over 24 hours. The difference in the drug release behavior can be attributed to the differences in ionic interaction between the oppositely charged ions and to the concentrations of the drug within the beads, which depends on the compositions of the formulation and the pH of the dissolution medium. The release of drug was controlled by the mechanism of the dissolution of DFNa in the dissolution medium and the diffusion of DFNa through the hydrogel beads.

Chitosan‐phosphorylated chitosan polyelectrolyte complex hydrogel as an osteoblast carrier

To simulate extra-cellular matrix, a novel three-dimensional scaffold of polyelectrolyte complex (PEC) hydrogel as an osteoblast carrier was synthesized. First, chitosan, a natural glycosaminoglycan, was modified by phosphorylation to obtain a water-soluble phosphorylated chitosan (P-content: 10.7 mass%). The PEC hydrogel was then formed from equal volumes of 0.173 mass% phosphorylated chitosan in water and 1 mass% chitosan in 1% (V/V) acetic acid solution. Rat osteoblasts were seeded in the hydrogel. The PEC hydrogel had a three-dimensional hierarchically-porous structure and good cytobiocompatibility for osteoblasts in vitro. It is concluded that the PEC hydrogel is a promising material as an osteoblast carrier.

Polyelectrolyte complex hydrogel composed of chitosan and poly(γ‐glutamic acid) for biological application: Preparation, physical properties, and cytocompatibility

AbstractPolyelectrolyte complex (PEC) hydrogels composed of chitosan as a cationic polyelectrolyte and poly (γ‐glutamic acid) (γ‐PGA) as an anionic polyelectrolyte were prepared from PEC dispersions based on a chitosan solution to which different amounts of γ‐PGA solutions were added to charge equivalency. The chemical structures of the PEC hydrogels were investigated by Fourier transform infrared spectroscopy. The physical properties, fixed charge concentration, crystallinity, mechanical properties, micromorphology, and swelling properties of the PEC hydrogels were also investigated. The total fixed charge concentration of the PEC hydrogels varied as a function of pH on the pK intervals between chitosan (pK = 6.5) and γ‐PGA (pK = 2.27). The isoelectric points (IEP) were shifted to a lower pH with a higher weight ratio of γ‐PGA to chitosan. The elastic modulus was decreased with the weight ratio increasing from 0 : 1 to 1 : 1 (γ‐PGA/chitosan) by ionic crosslinking between the amino groups of chitosan and the carboxyl groups of γ‐PGA. The results of the swelling study showed that the swelling properties of PEC hydrogels were more affected by the change in the elastic restoring force than by the change in the fixed charge concentration depending on the pH. Also, the cytotoxicity of the PEC hydrogels was investigated using normal human dermal fibroblast (NHDF) cell lines, and the results showed the PEC hydrogels were not toxic. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103:386–394, 2007

PH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate: swelling kinetics and drug delivery properties

Porous chitosan (CS) polyelectrolyte complex (PEC) hydrogel microspheres were prepared via either wet phase-inversion or ionotropic crosslinking with sodium tripolyphosphate (Na +-TPP) and dextran sulfate (DS). The resulting microspheres were characterized using scanning electron microscopy (SEM) and elemental analysis (EA). The controlled release behavior of ibuprofen (IBU) from these microspheres was investigated. The PEC microspheres were about 700–950 μm in diameter with large pores and open porous structure. The CS/TPP/DS microspheres resisted hydrolysis in strong acid and biodegradation in enzymatic surroundings. The swelling kinetics for CS microspheres was close to Fickian diffusion, whereas those for CS/TPP and CS/TPP/DS were non-Fickian. Furthermore, the equilibrium water content (EWC) and water diffusion coefficient ( D) increased with the pH of the media. The release profiles of IBU from CS/TPP/DS microspheres were slow in simulated gastric fluid (SGF, pH 1.4) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 6 h after changing media. Overall the results demonstrated that CS/TPP/DS microspheres could successfully deliver a hydrophobic drug to the intestine without losing the drug in the stomach, and hence could be potential candidates as an orally administered drug delivery system.

Biomimetic Synthesis of Apatite - Polyelectrolyte Complex (Chitosan - Phosphorylated Chitosan) Hydrogel as an Osteoblast Carrier

A novel three-dimensional scaffold of hydroxyapatite(HA)-polyelectrolyte complex (PEC) composite hydrogel was synthesized by a biomimetic method. PEC hydrogel was formed from equal volumes of 1% phosphorylated chitosan in water and 1% chitosan in 1% acetic acid solution. This PEC hydrogel was soaked in saturated Ca(OH)2 solution for 4 d and then in accelerated calcification solution (ACS) for 7 d, both at 37 oC. The PEC hydrogel was a nano-composite material with multiple levels of hierarchical porosity; hydroxyapatite (HA) crystals nucleated and grew on the fiber surfaces of the hydrogel; Rat osteoblasts were then seeded in this three-dimensional scaffold of HA-PEC composite hydrogel, the three-dimensional scaffold of HA-PEC hydrogel revealed excellent biocompatibility.

PH-response of chitosan, κ-carrageenan, carboxymethyl cellulose sodium salt complex hydrogels

We synthesized the polyelectrolyte complex hydrogel consisting of chitosan, κ-carrageenan, and carboxymethyl cellulose sodium salt (NaCMC) and investigated the swelling properties of the gel varying with carrageenan/NaCMC compositions. In a lower composition of carrageenan, heterogeneous gels were obtained indicating strong electrostatic interactions among these polyelectrolytes. Oppositely, in a higher composition of carrageenan, a gelation did not occur. It was cleared that a homogeneity of the gel strongly depended on the carrageenan/NaCMC composition. The degree of swelling at the equilibrium decreased proportional to the carrageenan composition. The gels showed a maximum degree of swelling in the range of pH 11–12. The maximum degree of swelling discontinuously decreased with increasing the NaCMC composition and was independent of the composition at a higher composition of NaCMC. Swelling properties in pure water and in alkaline solutions were also affected by salt concentrations of each polyelectrolyte aqueous solutions.

Study of biodegradation behavior of chitosan-xanthan microspheres in simulated physiological media.

Microspheres of a polyelectrolyte complex hydrogel were prepared from chitosan and xanthan after interaction between the two polyionic polymers. Their biodegradation was studied vs. chitosan. Simulated gastric fluid (SGF, pH 1.2) and intestinal fluid (SIF, pH 7.5) both as biodegradation media and phosphate buffered saline (PBS, pH 7.4) as a negative control were used. The degradation studies were performed at 37 degrees C at 240 rpm permanent stirring to mimic the physiologic conditions. High performance liquid chromatography (HPLC) was carried out to quantify the chitosan degradation products using glucosamine (GA) and N-acetyl-D-glucosamine (N-Ac-GA) as references. The peaks area integration method was used to determine the amount of each degradation product as a function of incubation time in the media. The effect of the media on the morphological structure of microspheres was assessed by scanning electron microscopy. From HPLC studies, it appeared that in SGF and SIF the major degradation products were glucosamine (GA) and N-acetyl-D-glucosamine (NAc-GA). In the first 15 days, oligochitosan fractions were released from the complex, whereas N-acetyl-D-glucosamine was detected in the media after this period. The degradation kinetics were assessed by the measurement of the cumulative degradation products, which showed faster degradation of chitosan than the complex in SGF and SIF. SEM micrographs showed an enhancement of microsphere porosity as a function of incubation time in the simulated physiological media. Our results suggest a better control of the degradation kinetics when chitosan is complexed to xanthan.

Transport of monocharged ions through environment-sensitive composite membranes based on polyelectrolyte complexes

Studies were made of transport features of composite membranes (CM) made from Millipore nitrocellulose acetate ultrafilters (pore diameter 0.05 μm), impregnated with a polyelectrolyte complex (PEC) based on poly(acrylic) acid, poly(ethylenepiperazine) and poly(ethyleneimine). The H + ion diffusion rate depended on the starting pH, while the value of effective permeability dropped from 4.5 × 10 −6 to 2.6 × 10 −7 cm 2/sec when the starting pH was raised from 1.45 to 2.70. The dependence of CM permeability on H + ion concentration seems to be due to the presence of fixed ion-exchange groups in CM pores. At pH > 7 the CM hydraulic permeability ( L p) decreased abruptly, probably due to PEC hydrogel expansion in the ultrafilter pores, filling the pore space with dense gel. The rejection coefficient of OH −ions increased with the decrease of L p. Transport features of CM are analyzed in terms of diffusion in the “free” water volume as well as in surface water bound to ion-exchange groups.