N-methylated Chitosan Research Articles

Synthesis and Antimicrobial Activity of Silver N-Methyl Chitosan

This study synthesized silver N-methyl chitosan (Ag-NMC) and tested it for its antimicrobial and antifungal activity. Ag-NMC was characterized by FTIR, XRD, measured for its molecular weight (MW), solubility, and toxicity. The antimicrobial activity was tested by the agar diffusion method, determining the MIC (Minimum Inhibitory Concentration), MBC (Minimum Bactericidal Concentration) against Staphylococcus aureus and Escherichia coli bacteria, and determining the Minimum Fungicidal Concentration (MFC) against the fungus Candida albicans. The results showed that Ag-NMC had MW, solubility, and LC50 of 555.65 g/mol, 50 mg/mL, 945,492 mg/L, respectively. The diameter of the inhibition zone from the resulting diffusion test showed that Ag-NMC had better antimicrobial activity than N-methyl chitosan (NMC) and chitosan. The MIC, MBC, and MFC values of Ag-NMC were always lower than that of NMC and chitosan.

Amelioration of Physical Properties and Printability of Paper Coated with N-methylated Chitosan

In offset printing process, poor mechanical properties and printability of paper substrate usually result in printing problems, low quality of print and waste of paper materials. Therefore, many researches focus on the quality improvement of paper substrates using suitable additives. In this work, N-methylated chitosan, including N, N-dimethyl chitosan (DMC) and N, N, N-trimethyl chitosan (TMC), were prepared and employed as coating agents to ameliorate the mechanical properties and printability of paper sheets. Analysis results showed that the mechanical strength of coated papers with DMC and TMC were largely improved, because the fibers with negative charges were prone to form electrostatic bonding with the positively charged N-methylated chitosan, thus enhancing paper strength. Particularly, compared with chitosan and DMC, the TMC-coated paper exhibited better mechanical properties, printability and surface properties due to the high cationic charge density of TMC. Therefore, surface coating with TMC is of great benefit to decrease the printing problem of paper sheets and enhance the operation speed in offset printing. This work provides a valuable reference for the amelioration of the printability and physical properties of high-quality paper products for many promising applications.

Synthesis of N,N-Diethyl, N-Methyl Chitosan Chloride with Certain Quaternization Degree and Molecular Spectroscopic and Thermo-Morphological Study of the Alkylation

The quartenizeid chloride derivative of natural polyaminosaccharide chitosan was synthesized in two stages with acetate aldehyde and methyl iodide chemical reaction and ion replacement, which could be soluble in the water and wide pH ranges. The synthesis of the homopolymer was initially carried out with acetate aldehyde in Schiff reaction, and reduction was held on with the presence of NaBH4. The quaternization was accomplished in the acetonitrile medium with methyl iodine by continuous exposure of N2.7-8% quartenized N,N-diethyl, N-methyl chitosan iodine were synthesized with 89-91% yield, obtained by deprotonation of amine groups, with reaction of CH3J and N,N-diethyl chitosan. The ion exchange was carried out at 10% NaCl solution during 24 hours and N,N-diethyl, N-methyl chitosan chloride was obtained. Synthesis was performed with simpler and chemically effective methods compared to previous studies. The structure of product was characterized by FT-IR, UV-Vis, NMR, SEM, TGA, DTA and elemental analysis was determined. Functional changes in the structure of macromolecules were monitored with NMR and UV-Vis, and it was proved that, the main intermediate product was composed to be N,N-diethyl carbocation carrying >C=N-chromophore group. The increasing percent of carbon in content while alkylation is depeering and the presence of halogenated ions (Cl- or J-) after quaternization were observed. It has been determined that, the solubility of N,N-diethyl,N-methyl chitosan chloride or iodide in water and in pH =1-10 increased frequently. Key words. Chitosan; alkylation; diethylmethyl chitosan iodine; quartenization; UV-Vis; NMR

Synthesis, Characterization and Antifungal Activity of N-Methyl Chitosan and Its Application on the Gauze

Background: Chitosan is a natural polymer which has limited solubility. Chitosan is capable of being modified using multiple alternatives for chitosan chemical modifications that provide different desirable properties. Method: N-methyl chitosan was successfully prepared and characterized. N-methyl chitosan was characterized by the FTIR, XRD, SEM, TEM, solubility, water content, and specific surface area. Antifungal activity against Candida albicans of N-methyl chitosan and gauze coated N-methyl Chitosan were also determined in this study. The antifungal activity tests were performed using agar diffusion and broth microdilution methods. Gauze coating with N-methyl chitosan was performed with a pad-dry-cure method. The SEM photograph of N-methyl chitosan clearly showed the rugged nature of particles. The TEM image shows that N-methyl chitosan produced from synthesis possessed round shape, with an average diameter of 50 nm. Results: The results of solubility in water, water content, and specific surface of N-methyl chitosan were 2.04 mg/mL, 18.12%, and 0.995 m/g, respectively. Conclusion: N-methyl chitosan exhibited antifungal activity against C. albicans with MIC and MFC 0.75% and 1%, respectively. The maximum clear zone produced by gauze coated N-methyl chitosan occurred at 1% concentration of N-methyl chitosan, 60 seconds of dipping time, and 10 times of dipping frequency. Keywords: Chitosan, N-methyl chitosan, gauzed, antifungal activity, C. albicans, respiratory tract.

Comparative study on antimicrobial activity and biocompatibility of N-selective chitosan derivatives

N-selective derivatives of chitosan (CH) namely, N-methyl chitosan (NMC), trimethyl chitosan (TMC), diethyl methyl chitosan (DEMC) and carboxymethyl chitosan (CMC) were synthesized to study the effects of alkylation on antimicrobial property and biocompatibility. The derivatives were characterized by FT-IR confirming O-free alkyl substitution. XRD studies showed reduction in crystallinity and zeta potential measurement proved the increase in positive charges upon alkylation. Antimicrobial activity was observed to be in the order of DEMC<CMC<CH<NMC<TMC. MTT assay revealed that the modified chitosans were non-cytotoxic to primary normal human epidermal keratinocytes. Chitosan derivatives were tested using EpiDerm™ Skin Irritation Test as per OECD TG 439 and were categorized as non-irritants. Zebrafish embryo viability test was used to study the toxicity of the modified chitosans and LC50 for the samples in zebrafish embryo ranged from 20 to 50μg/mL. Results showed that amongst the alkyl derivatives, O-methyl free N,N,N–trimethyl chitosan (TMC) is the potential candidate material with enhanced antimicrobial property and biocompatibility. Herein, we report the first results of using chitosan or its derivatives in the EpiDerm in vitro skin irritation test. The four derivatives of chitosan are compared on a single platform for their physicochemical, biological and biocompatible properties.

Alternative Approach to Synthesize Methylated Chitosan Using Deep Eutectic Solvents, Biocatalyst and “Green” Methylating Agents

Conventional synthesis of N-methylated chitosan involves the use of organic solvents in alkaline conditions, using methyl iodide as the methylating agent. However, the method does not result in selective N-methylation and is known to cause heavy polymer scission. In this investigation, we have reported alternative “green” approaches for methylated chitosan synthesis. Two types of deep eutectic solvents (DESs), viz., DES(Urea) and DES(Gly), either alone or in combination with other solvents, were screened as media for facilitating the methylation of chitosan. Our results indicated that DESs mediated selective N-methylation in the absence of NaOH, with no polymer scission, when compared with the reported methods. 1H NMR spectra confirmed selective N-methylation in the case of products obtained using DES(Urea), while that obtained using DES(Gly) demonstrated some O-methylation. Another green method investigated the unexplored property of biocatalyst lipase for methylating chitosan in the presence of “green” ...

Advanced fibroblast proliferation inhibition for biocompatible coating by electrostatic layer-by-layer assemblies of heparin and chitosan derivatives

Heparin and different chitosan derivatives were applied to produce stable electrostatic layer-by-layer assemblies and further used as coating technique to inhibit natural inflammatory response to implants. Heparin was assembled with chitosan and N-methylated chitosan derivatives, namely N,N-dimethyl chitosan (DMC) and N,N,N-trimethyl chitosan (TMC), by dipping method. DMC and TMC (chitosan derivatives) were synthesized and characterized before LbL assembly. Ellipsometry, quartz crystal microbalance (QCM-D), and contact angle were used to demonstrate the deposition of polyelectrolyte multilayers onto silicon wafers using polyelectrolyte solutions with different ionic strength. The biological properties of these films were evaluated by cell culture assays using NIH/3T3 fibroblast cells. LbL assemblies of Heparin and chitosan derivatives showed to be biocompatible, and at the same time they strongly hinder the proliferation speed of fibroblasts up to 40-fold factors. Therefore, the multilayers prepared from heparin and chitosan derivatives have good features to be used as an alternative coating treatment for biomedical implants with reduced body rejection properties.

Chitosan and N-Alkyl chitosan as a heterogeneous based catalyst in the transesterification reaction of used cooking oil

This paper explains the result of research on the use of chitosan and N-alkyl chitosan (N-methyl chitosan, N-isopropyl chitosan) as a heterogeneous base catalyst in the transesterification reaction of used cooking oil. N-methyl chitosan and N-isopropyl chitosan synthesized by reacting chitosan with formaldehyde and acetone successively forming Schiff bases were then reduced using NaBH4. Then chitosan, N-methyl chitosan, N-isopropyl chitosan are used as heterogeneous catalysts in the transesterification reaction of used cooking oil. The results show that inclusion of alkyl groups to the chitosan structure leads to increase the amount of base in which chitosan, N-methyl chitosan, and N-isopropyl chitosan are 0.066 mole.g-1, 0.0068 mole.g-1, 0.0070 mole.g-1 respectively. It is also evident from the increasing yield of methyl esters. N-isopropyl chitosan gives the greatest content of methyl esters yield.

N-Diethylmethyl chitosan for gene delivery to pancreatic cancer cells and the relation between charge ratio and biologic properties of polyplexes via interpolations polynomial

In gene therapy of pancreatic cancer, non-viral vectors show an important role. These vectors are modified with the aim of improvement for pancreatic cancer gene therapy. For this aim, we used N,N-diethyl N-methyl chitosan (DEMC) for gene delivery to human pancreatic cancer cells (AsPC-1). pEGFP (Enhanced green fluorescent protein plasmid) was used as a model plasmid. In order to evaluate the efficiency of this polymer for gene delivery, the DEMC/pEGFP complexes are characterized via photon correlation spectroscopy, gel electrophoresis, fluorescence microscopy, flow cytometry and MTT assay. Also cancer cells’ mean fluorescence intensity (MFI) and size changes after transfection are evaluated. The enhancement in polyplexes’ charge ratios from 5 to 40, results in 16.70-fold increase in transfection efficiency. Higher MFI, cell size and cytotoxicity were observed as the N/P ratio increased. Considering that mathematical models can be used to understand and predict consequences associated with nanomedicine, the relation between DEMC/pDNA complexes charge ratio, cell transfection and toxicity was evaluated for the first time with Lagrange's interpolation polynomial method.

Release behavior of microspheres from cross-linked N-methylated chitosan encapsulated ofloxacin

Abstract A series of hollow microspheres encapsulated with ofloxacin have been successfully prepared, using cyclohexane droplets as a template and the N-methylated chitosan (NMC) cross-linked with glutaraldehyde as the shell. The structure and morphology were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The swelling and releasing behaviors of the microspheres having different weight-average molecular weights (Mw) and the degree of quaternization of NMC at pH 1.2 and 7.4 media were investigated. The results revealed that microspheres exhibited a very smooth surface, and electrostatic interaction existed between cross-linked NMC and ofloxacin. Ofloxacin encapsulated in the microspheres was rapidly released into phosphate buffer solution (pH 7.4), whereas it was only slowly released in 0.1 M HCl (pH 1.2). The degree of swelling of microspheres at pH 7.4 was higher than that at pH 1.2. Moreover, ofloxacin was released more slowly from the microspheres having high Mw of NMC than that with low Mw. The release mechanism of the hollow microsphere was proposed to be a non-Fickan diffusion through the swollen microspheres, and to be controlled by the Mw and the cross-linking density of shell.

Surface Fabrication of Hollow Microspheres from N-Methylated Chitosan Cross-Linked with Gultaraldehyde

We have successfully prepared biocompatible and biodegradable hollow microspheres with sizes between 2 and 5 mum using cyclohexane droplets as a template and the N-methylated chitosan (NMC) cross-linked with glutaraldehyde (GA) as the shell. The structure, morphology, and formation process of the hollow microspheres were characterized by FT-IR, (1)H and (13)C NMR, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results revealed that the microspheres exhibited a very smooth and hollow structure. This work confirmed that the hollow microspheres were accomplished by fabricating on the basis of chemical cross-linking on the surface of the emulsion droplets and by removing cyclohexane as core. The results from SEM and TEM indicated that the emulsion droplets covered with cross-linked NMC in the oil-in-water system aggregated together to form a precipitate of microspheres by coagulating with acetone. Moreover, the cross-linked NMC on the surface of the microspheres continuously cured to form the tight shell, whereas the inner area became a cavity with increase of the aging time, leading to the hollow microspheres. In addition, an anti-infective drug, ofloxacin (Floxin), encapsulated in the microspheres more rapidly released to reach 90 wt % at pH 7.4 within 8 h than at pH 1.2.

N,N-Diethyl N-Methyl Chitosan as an Enhancing Agent for Colon Drug Delivery

Chitosan exhibits poor solubility above pH 6 which prevents absorption at treatment sites in the colon. pH titrations and infrared methods were used to determine the degree of deacetylation of the starting chitosan. In the present work, N,N-diethyl N-methyl chitosan (DEMC) was synthesized based on a modified two-step process via a 22 factorial design to optimize the preparative conditions. DEMC chloride was characterized using FTIR and 1H NMR spectroscopy. For pharmacological and pharmaceutical applications, DEMC needs to have specific degrees of quaternization. Based on the 1H NMR data, a high degree of quaternization was achieved by the two-step process. The N-diethyl methyl chitosan chlorides were completely soluble in water at room temperature. Sodium fluorescein and brilliant blue were used as model reagents for in vitro colonic absorption studies. These studies show a significant increase in the absorption of sodium fluorescein and brilliant blue in the presence of DEMC in comparison with normal chitosan. DEMC with positive charge is able to interact with tight junctions of colon epithelial cells and hence increased the permeability of sodium fluorescein and brilliant blue across the tight junctions. These investigations demonstrated that the DEMC derivative of chitosan could have a significant effect on colonic drug absorption.

Multiple crystalline morphologies of N -Alkyl chitosan solution cast films

In addition to spherulites, two novel crystalline morphologies, i. e. need-like crystal and sheet-like crystals were found in formic acid solution cast films of N-methyl chitosan and N-ethyl chitosan during casting at 25°C and relative humidity 65%. Their size was larger in 1∼2 order of magnitude than chitin needle-like single crystals and chitosan lamellar single crystals reported previously due to the high molecular weight. The formation mechanism of these crystalline morphologies was discussed.