Derivatives of Chitosan

The reactive hydroxy and amino groups of chitosan have been used for its derivatization or chemical modification. The amino group being nucleophilic in nature allows easy formation of imine bond with aldehyde or corresponding amide derivatives. However, in acidic solution, the cationic property of chitosan is revealed and the amino groups act like alkali, receive protons, and generate salts [87]. Some of the derivatives with their method of syntheses have been summarized in Table 15.2. 

Inhibitor of hemagglutination of human erythrocytes by influenza virus 

Quaternized Aromatic Derivatives of Ch [Methylated [aminobenzyl] Ch Methylated [pyrid5myl) Ch Methylated [benzyl] Ch] 1% acetic acid + 1 N NaOH + corresponding aldehydes [4-fll,Al-dimethylbenzal-dehyde 4-P3U-idin carbaldehyde 4-Benzaldehyde] [48] 

Ch sulfates Chlorosulfonic acid-sulfuric acid + Dimethyl Formamide/ [22] [24] 

Fatty acid Stearic acid, + acetic acid [27] Development of 

---

More recently chitosan polymers which are derivatives of chitin materials have evoked interest due to their bioactivity and biodegradability. For example, N-carboxybutyl chitosan has been show to effectively promote wound healing (9). Acetate, and butyrate derivatives of chitosan have decreased blood clotting time significantly (10). 

Inclusion compounds have been reported from derivatives of chitosan 181) and from collagen 182) but structural information on these is unavailable at present. 

The complexing of chitosan and its basic derivatives with anionic substances is paralleled by compatibility with cationic and nonionic compounds. Similarly, the anionic derivatives of chitosan show complex formation with cationic agents and are compatible with anionic and nonionic compounds. The capability of these chitosan derivatives to complex with certain metal ions, notably those of the transition series, is also important, having possibilities for the removal of metal salts from effluent. The hierarchy in terms of binding capacity is Cr(III) < Cr(II) < Pb(II) < Mn(II) < Cd(II) < Ni(II) < Fe(II) < Co(II). 

The novel L-lysine modified cross-linked chitosan resin containing imine linkers [15] has been studied by the 13C CP MAS spectroscopy.31 However, as some ambiguous results were obtained and the resin was insoluble, instead of the resin a soluble model compound, derivative of chitosan oligosaccharide, has been obtained and investigated. 

Just recently a series of other quaternized chitosan derivatives have been synthesized and characterized, namely, A,A-dimethyl, A-ethyl chitosan (DMEC) (Bayat et al. 2006), A-methyl, A,A-diethyl chitosan (DEMC) (Avadi et al. 2004) and A,A,A-triethyl chitosan (TEC) (Avadi et al. 2003). In a comprehensive study (Sadeghi et al. 2008a, b) the four quaternized derivatives of chitosan, trimethyl chitosan (TMC), diethylmethyl chitosan (DEMC), triethyl chitosan (TEC) and dimethylethyl chitosan (DMEC) with degree of substitution of approximately 50% were synthesized and their effect on the permeability of insulin across intestinal Caco-2 monolayers was studied and compared with chitosan both in free-soluble form and in nanoparticulate systems. Trans-epithelial electrical resistance (TEER) studies revealed that all four chitosan derivatives in free-soluble forms were able to decrease the TEER value in the following order TMC>DEMC>TEC = DMEC>chitosan, indicating their... 

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],... 

Zhang J, Wang Q, Wang L, Wang A (2007) Manipulated dispersion of carbon nanotubes with derivatives of chitosan. Carbon 45 1911-1920... 

A-(2-Hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is a water-soluble derivative of chitosan (CS), synthesized by the reaction between glycidyl-trimethyl-ammonium chloride and CS. HTCC nanoparticles have been formed based on ionic gelation process of HTCC and sodium tripolyphosphate (TPP). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the HTCC nanoparticles. HTCC nanoparticles were 110-180nm in size, and their encapsulation efficiency was up to 90%. In vitro release studies showed a burst effect, followed by a slow and continuous release. Encapsulation efficiency was obviously increased with increase in initial BSA concentration [15]. 

A water soluble quaternary ammonium derivative of chitosan (N-(2-hydroxy)propy 1-3 -trimethylammonium chitosan chloride, HTCC) was used as an antimicrobial agent for cotton fabrics. HTCC had a lower minimum inhibition concentration against Staphylococcus aureirs, Klebsiella pneumoiniae and Escherichia coU compared with that of chitosan, but the antimicrobial activity was lost on laundering. However, when cotton fabrics were treated simultaneously with HTCC and polycarboxylic acids (particularly butanetetracarboxylic acid) (BTCA),... 

FIG. 6 Production of mercaptan derivatives of chitosan via conversion with 1-chloro-2,3 -epoxypropane. 

Among the many chemical derivatives of chitosan mentioned in literature [38], one can differentiate the specific reaction involving the -NH group at the C-2 position, or the non-specific reactions of -OH groups at C-3 and C-6 positions (especially esterification and etherification). The more common and easier reactions involving the amino group at C-2 position are the quaternization and the reductive amination with aldehydes [39]. 

Four major groups of hydrophobically modified chitosan have been used as potential drug delivery carrier for poorly soluble drugs (1) steroid derivatives, (2) fatty acids derivatives, (3) aryl and alkyl derivatives, and (4) carboxymethyl derivatives of chitosan (Figs. 3-6). Others types of modified chitosan have also been synthesized [117-119]... 

Noh SM, Park MO et al (2010) Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA. J Control Release 145 159-164... 

Desbrieres J, Martinez C et al (1996) Hydrophobic derivatives of chitosan characterization and rheological behaviour. Int J Biol Macromol 19 21-28... 

Hirano, S., Tanaka, Y, Hasegawa, M., Tobetto, K., and Nishioka, A. (1985). Effect of sulfated derivatives of chitosan on some blood coagulant factors, Carbohydr. Res., 137, 205-215. 

Mahjub, R., Dorkoosh, F. A., Amini, M., Khoshayand, M. R., and Raflee-Tehrani, M. (2011). Preparation, statistical optimization, and in vitro characterization of insulin nanoparticles composed of quaternized aromatic derivatives of chitosan, AAPS PharmSciTech, 12 (4), 1407-1419. 

Acetoxybenzoyl (aspirin) derivatives of chitosan, -desulph-ated heparin, and D-glucosamlne have been synthesized and tested as pro-drugs for aspirin. 

Synthesis and characterization of novel water soluble derivative of chitosan as an additive for Polysulfone ultrafiltration membrane. J. Membr. Sci. 440 140-147. 

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. 

---