Carboxymethyl chitosan derivatives

Both, N-carboxymethyl and 0-carboxymethyl chitosan derivatives have been prepared under different reaction conditions using monochloroacetic acid in the presence of NaOH to achieve the N-versus-O selectivity [60, 61]. The selective route for synthesizing N-carboxymethylation utilizes glyoxylic acid in a reductive amination sequence [62], N-Carboxymethyl and 6-0-carboxymethyl chitosan... 

In general these derivatives are safe, their chemical functions being the glycine moiety the same holds for AT,0-carboxymethyl chitosan, as demonstrated for instance by studies intended to assess the efficacy of W,0-carboxymethyl chitosan to limit adhesion formation in a rabbit abdominal surgery model. The inability of fibroblasts to adhere to N,0-carboxymethyl chitosan-coated surfaces suggests that it may act as a biophysical barrier [135]. 

Thanou, M., Nihot, M.T., Jansen, M., Verhoef, J.C. and Junginger, H.E. (2001d) Mono— A-carboxymethyl chitosan (MCC), a polyampholytic chitosan derivative, enhances the intestinal absorption of low molecular weight heparin across intestinal epithelia in vitro and in vivo. J. Pharm. Sci. 90 38-46. 

Various chitosan derivatives of enhanced solubility, mucoadhesive, and permeation properties were developed. V-Trimethyl chitosan chloride (TMC) is a quater-nized derivative of chitosan with superior aqueous solubility over a broader pH range and penetration-enhancing properties under physiological conditions [78]. Carboxymethylated chitosan (CMChi) is a polyampholytic polymer able to form viscoelastic gels in aqueous environments. CMChi appears to be less potent compared with the quaternized derivative. Neither TMC nor CMChi have been found to provoke damage of the cell membrane, and therefore, they should not alter the viability of nasal epithelial cells [79],... 

Furusaki, E., Ueno, Y., Sakairi, N., Nishi, N., and Tokura, S. 1996. Facile preparation and inclusion ability of chitosan derivative bearing carboxymethyl-beta-cyclodextrin. Carbohydr. Polym. 9, 29-34. 

Chitosan derivatives have also been studied for possible utilization in wound dressings. For example, three kinds of chitosan derivative (oligochitosan, N,0-carboxymethyl-chitosan, and Al-carboxymethyl-chitosan) are used to form sheets and pastes, all of which exhibit appropriate cytocompatibility to the fibroblasts isolated from normal human dermis and hypertrophic scars [179]. 

In order to modify or enhance specific properties of chitosan, chemical derivatives have been synthesized by using the amines and hydroxyl groups in the molecular structure. Some examples include trimethyl chitosan, glycol chitosan, carboxymethyl chitosan, half-acetylated chitosan, and thiolated chitosan." ... 

Muzzarelli, R. A. A. and Tanfani, F. 1982. Af-(o-carboxybenzyl chitosan), Af-carboxymethyl chitosan and dithiocarbamate chitosan New chelating derivative of chitosan. Pure Appl. Chem. 54 2141-2150. 

Carboxymethyl chitosan succinamide Synonyms Chitosan, N-(3-carboxy-1-propanoyl)-, carboxymethyl derive. 

Chitosan, butoxylated. See Butoxy chitosan Chitosan, N-(carboxymethy)-. See Carboxymethyl chitosan Chitosan, N-(3-carboxy-1-propanoyl)-, carboxymethyl derive.. See Carboxymethyl chitosan succinamide Chitosan, 2,3-dihydroxypropyl-2-hydroxy-3-(trimethylammonio)propyl ether, chloride. See Polyquaternium-29... 

Chitosan-based nano- and microparticles are widely used for fabrication of controlled dmg release systems. Numerous studies have demonstrated that chitosan and its derivatives (A-trimethyl chitosan, mono-A-carboxymethyl chitosan, etc.) are effective and safe for absorption enhance to improve mucosal (nasal, peroral) delivery of hydrophylic macromolecules, such as peptide and protein dmgs as well as heparins [37,38]. This absorption enhancing effect of chitosan is caused by the opening of intercellular tight junctions, thereby favoring the paracellular transport of macro-molecular dmgs. Recently, a series of successful model chitosan-based polymer systems for mucosal dmg delivery have been reported. Thus, Lim et al. [39] have proposed novel polymer microparticles based on combination of hyaluronic acid and chitosan hydroglutamate... 

Muzzarelli R.A.A., Tanfani F., JV-(O-Carboxybenzyl) chitosan, iV-carboxymethyl chitosan, and chitosan dithiocarbamate new chelating derivatives of chitosan. Pure Appl. Chem., 54(11), 1982,2141-2150. 

Xie et al. (2001) have reported that the water-soluble chitosan derivatives prepared by graft copolymerization of maleic acid sodium onto hydroxypropyl chitosan and carboxymethyl chitosan sodium, exhibit scavenging activities against hydroxyl radicals. 

FIGURE 25.1 Chemical structures of chitin and chitosan derivatives which have been utilized as immuno-adjuvants (A) chitin (B) chitosan (C) triuiethyl chitosan (D) mono-A-carboxymethyl chitosan. 

CM-chitosan is a kind of carboxymethylated derivative of chitosan, which is prepared by the chemical reactions of chitosan and monochloroacetic acid. It contains -COOH and -NH2 groups in the molecular structure. Being a soluble chitosan derivative in both acidic and basic physiological media, it might be a better candidate than chitosan for studying the mechanism of degradation reaction of chitosan derivatives. 

Davies DH, Elson CM, Hayes ER. lV,0-Carboxymethyl chitosan, a new water soluble chitin derivative. In Skjak-Braek G, Anthonsen T, Sandford P, eds. Chitin and Chitosan Sources, Chemistry, Biochemistry, Physical Properties and AppUcations. London Elsevier Apphed Science, 1989 467-472. 

Chemical. A large number of chitin and chitosan derivatives have been synthesized through modification of the primary (C-6) and secondary (C-3) hydroxyl groups present on each repeat imit, including amine (C-2) functionality existing on deacetylated imits (31). Reactions typical of hydroxyl and amine groups (such as acylations with acid chlorides and anhydrides) including urethane and urea formation respectively, are feasible with isocyanates. The primary amine can be quatemized by alkyl iodides or converted to an imine with a variety of aldehydes and ketones that can subsequently be reduced to an N-alkylated derivative. Chitin and chitosan are reactive with a variety of alkyl chlorides after treatment with concentrated NaOH. Important derivatives such as carboxymethylated chitin and chitosan are commonly produced in this manner with the addition of sodium chloroacetate. 

Recent research explored various chemically modified conjugates and derivatives to improve its physico-chemical and biological properties. This modification allows significant applications of chitosan in various disciplines of biomedical research. So far various fabrication methods have been employed for the development of chemically modified chitosan e.g. chitosan-poly(acrylic acid) nanoparticles and acylated chitosan nanoparticles have been recently explored to examine their modifications effect on physicochemical properties and blood compatibility [151, 152], Similarly self-aggregated NPs of cholesterol-modified 0-carboxymethyl chitosan conjugates were fabricated to improve the pharmaceutical and biomedical applications of chitosan [153], Various examples of chitosan and its chemically modified synthetic derivatives are mentioned in Table 3.2. 

To overcome these limitations, chitosan has turned out to be a promising candidate as it sufficiently encapsulates the biomacromolecules and helps in their paracel-lular transport across the biological surface. Chitosan and some of its water-soluble derivatives such as N-trimethyl chitosan and mono-N-carboxymethyl chitosan have been used for improving the nasal and peroral absorption of various proteins, peptides and heparins via paracellular transport across the mucosa by opening the intercellular junctions [144-146]. 

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