Methyl Chitosan Research Articles

Diethyl methyl chitosan as an intestinal paracellular enhancer: ex vivo and in vivo studies

Chitosan exhibits favorable biological properties such as no toxicity, biocompatibility and biodegradability; therefore, it has attracted great attention in both pharmaceutical and biomedical fields. Chitosan exhibits poor solubility at pH values above 6 that prevents enhancing effects at the sites of absorption of drugs. In the present work, N-diethyl methyl chitosan (DEMC) was prepared and the enhancing effect of this polymer was investigated. Ex vivo studies have shown a significant increase in absorption of brilliant blue in the presence of diethyl methyl chitosan in comparison with chitosan. DEMC with positive charges is able to interact with tight junctions of colon epithelial cells and hence increases permeability of brilliant blue across the tight junctions. In vivo investigations have exhibited the absorption enhancer effects of DEMC on the colon absorption of insulin in normal and diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect. A significant decrease in blood glucose was observed, when mixture of insulin and DEMC was introduced in ascending colon of rats.

Effect of Carboxy Methyl Chitosan on Experimental Osteoarthritis in a Rabbit Knee: Carboxy methyl chitosan vs. Hyaluronan

Purpose: This study evaluates the effect on carboxy methyl chitosan on the articular cartilage of an osteoarthritic knee. Materials and Methods: The biological effect of chitosan on the osteoarthritic articular cartilage was compared with hyaluronan, which is one of the treatment modalities for an osteoarthritic knee. Chitosan or hyaluronan were injected into the intraarticular space of the experimental osteoarthritic knee of a rabbit with a transected anterior cruciate ligament at weekly intervals for 5 weeks, and the articular cartilage and synovium were obtained. Nine weeks later, the specimens were analyzed by their gross findings, histological examinations, and histo-morphometric studies. Results: The hyaluronan and chitosan group showed less severe osteoarthritic changes than the control group. Although the hyaluronan group showed less severe osteoarthiricic changes than the chitosan group, there was no statistical significance. Conclusion: Carboxy methyl chitosan, which has an excellent affinity to the body, appeared to have an positive effect on delaying the progress of cartilage degeneration.

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.

Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs

The absorption enhancing effects of chitosan and its derivatives have been intensively studied in recent years. It has been shown that these compounds are potent absorption enhancers. Chitosan is only soluble in acidic environments and is therefore incapable of enhancing absorption in the small intestine, the main absorption area in the gastrointestinal tract. Special emphasis has been placed on the absorption enhancing properties of N -trimethyl chitosan chloride (TMC), a partially quaternised derivative of chitosan, due to its solubility in neutral and basic environments. TMC is prepared by the reductive methylation of chitosan. The degree of quaternisation can be altered by increasing the number of reaction steps or by increasing the reaction time. Although the molecular weight of the polymer increases with addition of the methyl groups, a net decrease in the molecular weight is observed due to a decrease in the chain length of the polymer. TMC, like chitosan, possesses mucoadhesive properties. In vitro studies performed on Caco-2 cell monolayers showed a pronounced reduction in the transepithelial electrical resistance (TEER). TMC is also able to increase the permeation of hydrophilic compounds such as [ 14 C]-mannitol and [ 14 C] polyethylene glycol 4000 ([ 14 C] PEG 4000, MW4000) across the cell monolayers. It was also shown that the degree of quaternisation of the polymer plays an important role on its absorption enhancing properties, especially in neutral environments where chitosan is ineffective as an absorption enhancer. The reduction in TEER is an indication of the opening of the tight junctions located between epithelial cells. Opening of the tight junctions will result in enhancement of absorption via the paracellular route. Confocal laser scanning microscopy confirmed transport of large hydrophilic compounds via the paracellular route as well as the mechanism of action of the polymer in which redistribution of the cytoskeletal F-actin is provoked, which leads to the opening of the tight junctions. Various in vivo studies in different animal models confirmed the ability of TMC to increase the absorption of the peptide drugs buserelin and octreotide after intraduodenal or -jejunal administration. However, TMC has always been administered as a solution in these studies. The impracticality of administering a solution, as well as the fact that most peptides are unstable in the presence of water, have led to the need for a solid oral dosage form with which TMC can be administered together with peptide drugs. Recent studies have focused on the development and in vivo evaluation of solid oral dosage forms.

A kinetic study on the thermal degradation of N, N, N-trimethylchitosan

The thermal degradation of chitosan and N, N, N-trimethylchitosan, degrees of quaternization 5%, 21% and 33%, was studied by using TG in nitrogen atmosphere. The methylation of chitosan decreased its thermal stability, the decrease being more important the greater the degree of quaternization attained. The absolute values of the activation energy of chitosan and N, N, N-trimethylchitosan calculated from different methods, Broido's and MacCallum's methods, do not agree but they do show the same general trend. The activation energy for the less methylated derivative is higher than that of chitosan but it decreases as the degree of quaternization increases, independently of the method used for its determination. The use of the MacCallum's method reveals that the activation energy increases with increasing degree of conversion for chitosan but no clear trend is observed for the N, N, N-trimethylchitosans. The occurrence of a more complex set of reactions is suggested for the N, N, N-trimethylchitosan samples, including acid-catalyzed processes.

Influence of methylation process on the degree of quaternization of N-trimethyl chitosan chloride

N-Trimethyl chitosan chloride (TMC) is a soluble chitosan derivative that shows effective enhancing properties for peptide and protein drug transport across mucosal membranes. TMC was synthesized by reductive methylation of chitosan in an alkaline environment at elevated temperature. The number of methylation process steps and the base used in the process was demonstrated to affect the degree of quaternization of the primary amino group and methylation of 3- and 6-hydroxyl groups. 1H-Nuclear magnetic resonance spectra showed that the degree of quaternization of TMC was higher when using sodium hydroxide as the base compared to using dimethyl amino pyridine. The degrees of quaternization as well as O-methylation of TMC increased with the number of reaction steps. O-Methylation resulted in decreased solubility of TMC. The high degree of quaternization of TMC with a low degree of O-methylation was prepared by employing one reaction step with two subsequent addition steps and a controlled alkaline environment of the mixture reaction.

Methylation of Chitosan with Iodomethane: Effect of Reaction Conditions on Chemoselectivity and Degree of Substitution

AbstractN,N,N‐trimethylchitosan (TMC) was prepared by reacting purified chitosan with iodomethane, in the presence of sodium hydroxide, water and sodium iodide, at room temperature. The reaction medium was N‐methyl‐2‐pyrrolidone. Different samples of TMC were obtained by adding to the reaction medium a fixed volume (5.5 mL) of aqueous NaOH solutions at different concentrations (15, 20, 30 and 40 wt.‐%) and carrying out the reactions for 9 or 24 h. The features observed in the 1H and 13C NMR spectra of these chitosan derivatives, in respect of the chemical shift, number and relative intensity of the signals, depended strongly on the excess of NaOH and H3CI added to the reaction medium, but when the lowest excess was employed, the characteristics of the derivative were not affected by the reaction time to the same extent. The average degree of quaternization of these N‐methylated derivatives of chitosan ranged from 10.5% to 44.8%, according to the reaction conditions. Increasing the excess of NaOH, in reactions carried out for 9 h, resulted in TMC samples with progressively higher content of trimethylated sites however, the reaction yields were correspondingly lower and O‐alkylation was favored in these cases.1H NMR spectrum of sample [AX]24h dissolved in D2O (Cp = 10 g/L).magnified image1H NMR spectrum of sample [AX]24h dissolved in D2O (Cp = 10 g/L).

New Selectively N-Substituted Quaternary Ammonium Chitosan Derivatives

New chitosan derivatives were synthesized by N-selective introduction of quaternary ammonium-type side chains without protection of hydroxy groups, although direct quaternization of the amino group of chitosan using alkyl halides under alkaline conditions introduced alkyl groups not only to the amino group but also to the hydroxy groups. The reductive N-alkylation reaction of chitosan with quaternary ammonium-type aldehydes, such as 4-formyl-N-methylpyridinium iodide and [3-(4-formylphenoxy)propyl]trimethylammonium iodide, followed by anion-exchange reaction gave partially N-p-(N-methylpyridinio)methylated chitosan chloride (N-MP[Cl-]) and partially N-4-[3-(trimethyl-ammonio)propoxy] benzylated chitosan chloride (N-TMPB [Cl-]), respectively. From the viewpoint of utilization as antistatic material for functional textile, the electric resistance of newly prepared derivatives were investigated. In comparison with known quaternary ammonium chitosan derivatives (Q-CDs), such as 96% deacetylated chitin hydrochloride (DAC-96·HCl), partially O-methyl-N-trimethylated chitosan chloride (O-Me-N-TM[Cl-]), and partially N, O-(2-hydroxy-3-trimethylammonio) propylated chitosan chloride (N, O-HTMP [Cl-]), N-MP [Cl-]) showed the lowest specific resistance (ρ). N-TMPB [Cl-] whose ρ was comparable with that of N-TM [Cl-] showed lower water content compared with known Q-CDs noted above. Newly prepared Q-CDs thus appear as promising biocompatible antistatic materials.

Effect of surfactants on the stability of modified egg-yolk phosphatidyl choline liposomes

Disintegration by surfactants on egg-yolk phosphatidyl choline (PC) vesicles, stabilized with polycholesteryl methacrylate and carboxy methyl chitosan, was investigated by measuring the amount of marker dye (bromothymol blue) released from the vesicles. In all the studies at pH 7.4 anionic and nonionic surfactants caused vesicle disintegration at low concentrations while cationic surfactants produced breakdown of vesicles at high concentrations. It was found that the modified liposomes disintegrated in the following order: Polymeric liposomes less than carboxymethyl chitosan coated/stearic acid/oleic acid containing PC liposomes less than cholesteryl methacrylate monomer containing PC liposomes/PC liposomes Polymeric liposomes were found to be the most stable compared with all other types. This may be explained due to the filling of the pores in the lipid structure which in turn block the surfactant penetration into phospholipid bilayers. In contrast to unsaturated fatty acid (oleic acid) saturated fatty acid (stearic acid) containing liposomes are more stable.

Methylation Studies on Carboxyl-Reduced Heparin. 2-Amino-2-deoxy-3,6-di-O-methyl-α-D-glucopyranose from the Methylation of Chitosan1

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethylation Studies on Carboxyl-Reduced Heparin. 2-Amino-2-deoxy-3,6-di-O-methyl-α-D-glucopyranose from the Methylation of Chitosan1M. L. Wolfrom, J. R. Vercellotti, and D. HortonCite this: J. Org. Chem. 1964, 29, 3, 547–550Publication Date (Print):March 1, 1964Publication History Published online1 May 2002Published inissue 1 March 1964https://doi.org/10.1021/jo01026a006RIGHTS & PERMISSIONSArticle Views147Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (608 KB) Get e-Alerts Get e-Alerts