Carboxymethyl Chitosan Hydrogel Research Articles

Development of carboxymethyl chitosan hydrogel beads in alcohol-aqueous binary solvent for nutrient delivery applications

Carboxymethyl chitosan (CMCS) hydrogel beads were normally prepared from a composite formulation with other polymers, such as alginate. In present study, a novel method was developed to prepare CMCS hydrogel beads in alcohol-aqueous binary solvents. The morphology and shape of the beads were highly dependent on alcohol concentration. The most spherical hydrogel beads were obtained with 3% calcium and 30% alcohol concentration. The chemical crosslinking agent, glutaraldehyde, was needed to maintain the hydrogel integrity and morphology upon drying. Vitamin D3, a model nutrient, was encapsulated into the beads and 96.9% encapsulation efficiency was obtained. The effects of freeze-drying and room temperature drying were studied on the swelling behaviors and release properties in simulated gastrointestinal conditions. Possible mechanisms for CMCS hydrogel beads formation in binary solvents were discussed. The CMCS hydrogel beads prepared in 30% alcohol-aqueous binary solvent may be a promising delivery system for hydrophobic nutrients or drugs.

Synthesis and Characterization of Carboxymethyl Chitosan Hydrogel: Application as pH-Sensitive Delivery for Nateglinide

In current research, chitosan was reacted with mono-chloroacetic acid under alkaline condition to prepare carboxymethyl chitosan (CMCTs). The degree of substitution (Ds) on prepared CMCTs was found to be 0.68. CMCTs was used as a potential carrier for pH specific delivery of nateglinide after crosslinked using glutaraldehyde in presence of nateglinide. The average molecular weight and degree of deacetylation (DD) of chitosan were found to be 3.5x104 Da and 84.6% respectively. High yield (82%) and loading of drug (75%) were found in the developed hydrogel formulations. pH responsive swelling behavior of prepared hydrogels was checked using different pH values (1.2, 6.8 and 7.4). The study indicated very less swelling at pH 1.2 (for first 2 h) and quick swelling at pH 6.8 (for next 3 h) followed by linear swelling at pH 7.4 (for next 7 h) with slight increase. In vitro release profile of hydrogels showed biphasic release pattern dependent on swelling behavior. The release pattern was found to be non-fickian diffusion kinetics at higher pH. FTIR, 1H-NMR, DSC and p-XRD studies were carried out to confirm the formation of CMCTs, drug entrapment and its possible interaction in formulations. These studies revealed that no chemical change was found in nateglinide during preparation of hydrogel formulations. Scanning Electron Microscopy (SEM) was used to study the surface morphology of prepared hydrogels before and after dissolution which revealed pores formation after dissolution.

Synthesis and antimicrobial activity of some novel terephthaloyl thiourea cross-linked carboxymethyl chitosan hydrogels

Four novel hydrogels composed of carboxymethyl chitosan (CM-chitosan) cross-linked with various contents of terephthaloyl thiourea moieties (TTUCM-chitosan-1, TTUCM-chitosan-2, TTUCM-chitosan-3, TTUCM-chitosan-4) have been successfully synthesized. The hydrogels were characterized by elemental analyses, FTIR, 13C NMR, SEM, XRD, solubility and swell ability in various solvents. The antimicrobial activities of these hydrogels against three crop-threatening pathogenic fungi (Aspergillus fumigatus, Geotrichumcandidum and Candida albicans) and against three bacterial species (Bacillis subtilis, Staphylococcus aureus and Escherichia coli) were investigated. The hydrogels showed higher antibacterial activity than the parent CM-chitosan as judged by their higher inhibition zone diameter and lower minimum inhibition concentration. They are more active against Gram-positive bacteria than against Gram-negative bacteria. The results also indicated that the hydrogels have effective antifungal activity as compared with CM-chitosan. The antimicrobial activity of the hydrogels increased with increasing their cross-linking density.

Immobilization of a protease on modified chitosan beads for the depolymerization of chitosan

Abstract Neutral protease was immobilized on chitosan (CS), carboxymethyl chitosan (CMCS), and N -succinyl chitosan (NSCS) hydrogel beads. And the biocatalysts obtained were used to prepare low molecular weight chitosan (LMWC) and chitooligomers. Weight-average molecular weight of LMWC produced by neutral protease immobilized on CS, CMCS and NSCS hydrogel beads were 3.4 kDa, 3.2 kDa and 1.9 kDa, respectively. The effects of immobilization support and substrate on enzymatic reaction were analyzed by measuring classical Michaelis–Menten kinetic parameters. The FT-IR, XRD and potentiometric determination results indicated decrease of molecular weight led to transformation of crystal structure, but the degree of N -deacetylation and chemical structures of residues were not changed compared to initial chitosan. The degree of polymerization of chitooligomers was mainly from 2 to 7. We observed a strong dependence of the immobilized enzyme properties on the chemical nature of the supports, which leads to different microenvironment of neutral protease and changes the hydrolyzing process.

Crosslinked poly(vinyl alcohol)/carboxymethyl chitosan hydrogels for removal of metal ions and dyestuff from aqueous solutions

AbstractHydrogels composed of poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMCh) were synthesized via ultraviolet (UV) irradiation that can be used in several industrial fields. Several analysis tools were used to characterize the physical and thermal properties of CMCh/PVA hydrogels namely FT‐IR, scanning electron microscope (SEM), XRD, thermogravimetric analysis (TGA), and differential scanning calorimetery (DSC). TGA results showed that CMCh/PVA hydrogels are thermally more stable than CMCh and their thermal stability increases as PVA content increases in the hydrogel. Also, DSC results showed that CMCh/PVA hydrogels are at least partial miscible blends. Moreover, the swelling behavior of the CMCh/PVA hydrogels was studied in different buffered solutions and in different salt solutions at various concentrations. CMCh/PVA hydrogels swell much more than CMCh especially at alkaline pH. Both metal and dye uptake were studied for CMCh/PVA hydrogels. The hydrogels adsorb much more dyestuff and metal ions like Cu2+, Cd2+, and Co2+ than CMCh itself. Much dyestuff and metal ions are adsorbed by the hydrogels as PVA content increases in the hydrogel. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Controlled release of berberine hydrochloride from alginate microspheres embedded within carboxymethyl chitosan hydrogels

AbstractBerberine hydrochloride is a natural medicine with wide clinical application. In this article, berberine hydrochloride was entrapped into alginate microspheres via an emulsification/gelation method. The size distribution of the microspheres was determined by a laser particle sizer. Drug distribution within the microspheres was determined by confocal laser scanning microscopy. Those drug‐loaded microspheres were further entrapped into carboxymethyl chitosan (CMC) hydrogel to form a new drug‐delivery system (DDS). The surface morphology of the DDS was observed using metallographic microscopy and scanning electron microscopy (SEM). The compression strength of the DDSs with alginate microspheres was found significantly higher than that of the pure hydrogel. The drug‐release performances of the DDS in phosphate buffer solution (PBS, pH 7.4), saline solution (pH 6.3), and hydrochloric acid solution (HAS, pH 1.2) were also studied. Decay of the DDS in PBS within 72–80 h results in a faster release; however, the steady release in saline solution could last for all the testing period without cleavage of the DDS. In HAS, because of the shrinkage of the DDS, release is fast in the first period and remains steady later. The DDS exhibits prospective in controlled steady release of drugs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Thermo‐ and pH‐sensitive poly(vinylmethyl ether)/carboxymethylchitosan hydrogels crosslinked using electron beam irradiation or using glutaraldehyde as a crosslinker

AbstractBACKGROUND: Stimuli‐sensitive or intelligent hydrogels have been investigated for many biomedical and pharmaceutical applications. Those hydrogels with dual sensitivity will have more extensive potential applications. The aim of the work presented was to prepare a series of thermo‐ and pH‐sensitive hydrogels based on poly(vinylmethyl ether) (PVME) and carboxymethylchitosan (CMCS). The hydrogels were crosslinked using electron beam irradiation (EB) or using glutaraldehyde (GA) as a crosslinker at room temperature.RESULTS: The structures of the PVME/CMCS hydrogels obtained using the two crosslinking methods are proposed. The effects of component polymer ratio, GA content, irradiation dose, temperature and pH on the swelling behavior of the PVME/CMCS hydrogels were studied. There is a sharp decrease in the swelling ratios when the temperature increases from 25 to 37 °C. At low pH and also at high pH, the hydrogels have a higher swelling ratio; however, deswelling occurs evidently at a pH of around 3.CONCLUSION: The study shows that both EB and GA crosslinked hydrogels are thermo‐ and pH‐ sensitive, simultaneously. Thus, they may be potential candidates for both thermo‐ and pH‐sensitive applications. Copyright © 2009 Society of Chemical Industry

Preparation and properties of core–shell alginate–carboxymethylchitosan hydrogels

AbstractBACKGROUND: Hydrogels of alginate (ALG) with partially carboxymethylated chitosan (CMCHI) have been produced for drug delivery, based on the interactions between the negative groups and an ionic crosslinker. In the present work, CMCHI was used to evaluate the influence of amino groups that are positively charged at pH = 4 and 6 on the ALG–CMCHI core–shell hydrogel preparation. An ANOVA statistics tool was used to evaluate the effect of composition, pH and chitosan chemical nature on the morphology and swelling properties of the hydrogels in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF).RESULTS: The ALG–CMCHI core–shell hydrogels presented smaller (ca 2.3 µm) and more homogeneous microparticles than those with unmodified chitosan (ca 5.5 µm). The ALG–CMCHI hydrogels showed higher thermal stability and lower degree of swelling in SGF (314%) compared to those with chitosan (708%), since in the former hydrogels the protective layers that surround the particles are negatively charged.CONCLUSION: CMCHI can replace chitosan in the production of core–shell hydrogels with improved properties since the negative charge surrounding the ALG–CMCHI particles favours a lower degree of swelling. The results point out a possible prevention of burst release in SGF, sustaining the swelling ability of the ALG–CMCHI core–shell hydrogels in SIF, promising appropriate drug release. Copyright © 2009 Society of Chemical Industry

Synthesis and properties of carboxymethylchitosan hydrogels modified with poly(ester-urethane)

Preparation and properties of carboxymethylchitosan (CMC) modified with polyurethane (PU) containing poly(ethylene adipate) (PEA) as a soft segment is described. Urethane prepolymer was first synthesized by the reaction of PEA with an excess of 1,6-hexamethylene diisocyanate (HDI) to terminate its ends with isocyanate functional groups, followed by chain extension reaction using ethylene glycol as a chain extender. Its chemical structure was characterized by 1H NMR and FTIR, molecular weight by GPC, and thermal behavior by DSC. To prepare PU-modified CMC (CMC-PU), 1–60 wt% of PU were introduced into the CMC solution of THF:H 2O mixture (50:50 v/v) in the presence of 10 wt% of hexamethylene-1,6-di-(aminocarboxysulfonate) (HDA) to increase network density. Formation of the network structure was confirmed by investigating percent crosslinking and water swelling properties of CMC-PU compared to CMC network without PU. When percent of PU increased from 1 to 60 wt%, percent crosslinking of CMC-PU gradually increased up to 82%, whereas equilibrium water content (EWC) dropped and retained at 1000%. SEM showed microphase separation of PU (10–50 μm) thoroughly dispersed in CMC surface and in the bulk. In addition, CMC-PU exhibited a slight enhancement in toughness properties. Cytotoxicity and biocompatibility tests indicated that CMC-PU was non-toxic.

Platinum and palladium ions adsorption at the trace amounts by radiation crosslinked carboxymethylchitin and carboxymethylchitosan hydrogels

AbstractAdsorption of palladium and platinum ions at the trace amounts onto radiation crosslinked carboxymethylchitin (CMCht) and carboxymethylchitosan (CMChts) has been investigated. Maximum adsorption capacities for palladium were 2.679 and 1.053 mg/g dry gel, whereas for platinum they were 2.513 and 1.155 mg/dry gel for CMCht and CMChts, respectively. Retention capacity values for palladium were 0.45 and 0.06; for platinum 0.25 and 0.11 mEquiv./g for CMCht and CMChts, correspondingly. It has been shown that adsorption of Pd and Pt ions onto both hydrogels were dependent on the chloric and nitric ions concentration. Desorption experiments in HCl and HNO3 solutions proved that adsorption is governed by chelating mechanism rather than ion‐exchange one. SEM‐EDX spectroscopy showed that palladium and platinum ions were homogeneously distributed in all sections of hydrogel matrix. DSC experiments demonstrated decreasing in the decomposition temperature of polymers after inclusion of palladium and platinum ions, suggesting that metals are causing lowering of stability in polymer structural integrity. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 4015–4023, 2007

Calcium‐carboxymethyl chitosan hydrogel beads for protein drug delivery system

AbstractIn this study, carboxymethyl chitosan (CMC) hydrogel beads were prepared by crosslinking with Ca2+. The pH‐sensitive characteristics of the beads were investigated by simulating gastrointestinal pH conditions. As a potential protein drug delivery system, the beads were loaded with a model protein (bovine serum albumin, BSA). To improve the entrapment efficiency of BSA, the beads were further coated with a chitosan/CMC polyelectrolyte complex (PEC) membrane by extruding a CMC/BSA solution into a CaCl2/chitosan gelation medium. Finally, the release studies of BSA‐loaded beads were conducted. We found that, the maximum swelling ratios of the beads at pH 7.4 (17–21) were much higher than those at pH 1.2 (2–2.5). Higher entrapment efficiency (73.2%) was achieved in the chitosan‐coated calcium‐CMC beads, compared with that (44.4%) in the bare calcium‐CMC beads. The PEC membrane limited the BSA release, while the final disintegration of beads at pH 7.4 still leaded to a full BSA release. Therefore, the chitosan‐coated calcium‐CMC hydrogel beads with higher entrapment efficiency and proper protein release properties were a promising protein drug carrier for the site‐specific release in the intestine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3164–3168, 2007

Chitosaneous hydrogel beads for immobilizing neutral protease for application in the preparation of low molecular weight chitosan and chito‐oligomers

AbstractEnzyme hydrolysis with immobilized neutral protease was carried out to produce low molecular weight chitosan (LMWC) and chito‐oligomers. Neutral protease was immobilized on (CS), carboxymethyl chitosan (CMCS), and N‐succinyl chitosan (NSCS) hydrogel beads. The properties of free and immobilized neutral proteases on chitosaneous hydrogel beads were investigated and compared. Immobilization enhanced enzyme stability against changes in pH and temperature. When the three different enzyme supports were compared, the neutral protease immobilized on CS hydrogel beads had the highest thermal stability and storage stability, and the enzyme immobilized on NSCS hydrogel beads had the highest activity compared to those immobilized on the other supports, despite its lower protein loading. Immobilized neutral protease on all the three supports had a higher Km (Michaelis‐Menten constant) than free enzyme. The Vmax (maximum reaction velocity) value of neutral protease immobilized on CS hydrogel beads was lower than the free enzyme, whereas the Vmax values of enzyme immobilized on CMCS and NSCS hydrogel beads were higher than that of the free enzyme. Immobilized neutral protease on CS, CMCS, and NSCS hydrogel beads retained 70.4, 78.2, and 82.5% of its initial activity after 10 batch hydrolytic cycles. The activation energy decreased for the immobilization of neutral protease on chitosaneous hydrogel beads. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3743–3750, 2006

Adsorption of metal ions by carboxymethylchitin and carboxymethylchitosan hydrogels

Radiation cross-linking of CM-chitin and CM-chitosan has been investigated. Such parameters of radiation cross-linking as gelation doses, cross-linking and degradation radiation yields and ratios of scission to cross-linking has been determined for both polymers.The absorption ability of various metal ions into EB-radiation cross-linked carboxymethylchitin and carboxymethylchitosan has been investigated. The highest adsorption of scandium and gold has been obtained for carboxymethylchitin (CMCht) and carboxymethylchitosan (CMChts), respectively. Kinetic studies showed that adsorption of most of the metal ions occur in a relatively short period of time (2h). Detail investigation of adsorption of gold ions has been carried out for both hydrogels. The maximum uptake of Au cations, based on Langmuir equation was determined to be 37.59 for CM-chitosan and 11.86 for CM-chitin. Both hydrogels indicate favorable adsorption of gold cations.

New route to the preparation of carboxymethylchitosan hydrogels

A new method to prepare CM–chitosan hydrogels was introduced with the use of steam. The procedure was simple and economical, with no toxic chemicals involved. The steam-induced crosslinking of CM–chitosan sodium salt involved the –NH2 and –COONa groups, forming amide linkages (–CONH–), evidently supported by FTIR spectroscopy and other techniques. The hydrogels instantly imbibed a great deal of water. The degree of swelling (DS) of the hydrogels was found to be up to 36, depending on the harshness of steaming conditions used. Likewise, the coloration of the samples increased from light beige to brown with increasing temperature and duration of steam exposure. The overall efficiency of the steam method for the crosslinking of CM–chitosan sodium salt was quite high. The percentage weight loss was found to be less than 10 to obtain hydrogels with DS values around 20. No weight loss in the dry weight of the fractionated hydrogels was observed when the samples were steamed at 115°C or higher for 15 min or longer. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 4016–4020, 2003