Modification of Chitosan

Most chemical modifications of chitosan are performed at the free amino groups of the glucosamine units. There are also reports on modifications of chitosan hydroxyl 

Covalent modification of chitosan includes thiolation and hydrophobic modifications like acylation and quatemization, which will be discussed in later sections (Sections 7.1, 7.2 7.3). 

Transepithelial electrical resistance (TEER) measurements and transport smdies implied that CS/y-PGA NPs can be effective as an insulin carrier only in a limited area of the intestinal lumen where the pH values are close to the p/iTa of chitosan. So, a pH-responsive nanoparticle system was self-assembled by TMC and y-PGA for oral delivery of insulin. In contrast, TMC(40% Degree of Quatemisation) / y-PGA NPs may be a suitable carrier for transmucosal delivery of insulin within the entire intestinal tract. The loading efficiency and loading content of insulin in TMC/ y-PGA NPs were 73.8 2.9% and 23.5 2.1%, respectively. TMC/y-PGA NPs had superior stability in a broader pH range to CS/y-PGA NPs the in vitro release profiles of insulin from both test nanoparticles were significantly affected by their stability at distinct pH environments. TEER experiments showed that TMC/y-PGA NPs were able to open the tight junctions between Caco-2 cells, and this was further confirmed by confocal microscopy [66]. 

Various methods for preparation of chitosan nano/microparticles are emulsifica-tion/solvent evaporation, spray drying, ionotropic gelation and coacervation, emulsion crosshnking, sieving etc. 

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Chemical modifications of chitosan assayed to enhance cell specificity and transfection efficiency were reviewed. Also, chemical modifications of chitosan were performed to increase the stabihty of chitosan/DNA complexes [95]. 

H. Sashiwa, Y. Shigemasa, and R. Roy, Chemical modification of chitosan. 10.1. Synthesis of dendronized chitosan-sialic acid acid hybrid using convergent grafting of preassembled dendrons built on gallic acid and tri(ethylene glycol) backbone, Macromolecules, 34 (2001) 3905-3909. 

The only systems not listed in Tables 2-4 which are also likely to yield walled permeselective capsule are those based on polyvinylamine and chitosan. However, further research is required on the blending and processing of polyvinylamine systems, and the modification of chitosan, to enable the production of mechanically stable capsules which do not rupture catastrophically and slowly degrade as the present systems do under gelling with divalent ions. 

PEI grafting on chitosan is becoming a popular approach for modification of chitosan for gene delivery applications. In recent years several efforts to develop chitosan-g-PEI delivery vectors have been published. These include incorporation of mannose [117] and folic acid [118] derivatives for targeted delivery and application of chitosan-g-PEI for the delivery of siRNA [119]. 

Kim T-H, Jiang H-L, Jere D et al (2007) Chemical modification of chitosan as a gene carrier in vitro and in vivo. Prog Polym Sci 32(7) 726-753... 

Bernkop-Schnurch, A., Hornof, M. and Zoidl, T. (2003) Thiolated polymers- thiomers modification of chitosan with 2-iminothiolane. Int. J. Pharm. 260 229-237. 

The enzymatic treatment of chitosan in the presence of tyrosinase and phenol derivatives produced new materials based on chitosan.91 During the reaction, unstable o-quinones were formed, followed by the reaction with the amino group of chitosan to give the modified chitosan. The tyrosinase-catalyzed modification of chitosan with phenols dramatically altered rheological and surface properties of chitosan. The modification with chlorogenic acid onto chitosan conferred the water solubility of chitosan under basic conditions.92 A new water-resistant adhesive was developed by the tyrosinase-catalyzed reaction of 3,4-dihydroxyphenethylamine and chitosan.93 Poly(4-hydroxystyrene) was modified with aniline by using tyrosinase catalyst.94 The incorporated ratio of aniline into the polymer was very low (1.3%). 

Novel chitosan based catalytic systems for hydrogenation of unsaturated compounds in the liquid phase were prepared. The catalytic performance of the obtained systems depended significantly on the chitosan forms (as the micro beads or chitosan deposited on the mineral supports), their preparation method and chemical modification of chitosan as well. The obtained chitosan based carriers and catalysts were examined by transmission and diffuse-reflectance FTIR spectroscopy. 

Deposition of chitosan on SiOz (0.06-0.02 mm) and ZrOz was performed by multiple steeping of a portion of carrier in a solution of chitosan in 1% acetic acid and filtered. Wet or semi-dry chitosan-coated carrier was added directly to methanol or propanol-2 and stirred for 0.5-2h after addition of the calculated amount of glutaraldehyde. Calculated cross-linking extent was 10-15%. Chemical modification of chitosan was performed by carrier treatment with pyridinealdehyde-2 boiling solution in benzene. 

Table 3.4 Chemical modification of chitosan for improved reactivity.

Keywords Chitosan, modification of chitosan, biomedical applications... 

The first report on the modification of chitosan with sugars was by Hall and Yalpani [69-70].They synthesized sugar-bound chitosan by reductive M-alkylation with NaCNBHj using either an unmodified disaccharide (Figure 6.4, method A) or a monosaccharide-aldehyde derivative (Figure 6.4, method B). This type of modification has generally been used to introduce cell-specific sugars onto chitosan. 

However, low solubility, non-specificity, and low transfection efficiency of chitosan limited its clinical trials. Hence, chemical modification of chitosan became necessary to overcome its drawbacks for the clinical trials. 

Several chemical modifications of chitosan have been tested to make the solubility and/or positive charge of chitosan independent of pH. 

Chitosan has three types of reactive functional groups that allow modifications of chitosan to produce various useful hydrogels for tissue engineering applications [146]. 

The chemical modifications of chitosan described are not exhaustive but clearly demonstrate their benefit for drug delivery. Similarly, besides the described improvements in delivery of genes or poorly soluble drugs and in scaffolds for tissue engineering, other improvements in the delivery of therapeutic peptide and proteins or vaccines using chitosan-based systems have also been reported. 

Klaykruayat, B., Siralertmukfiil, K., and Sirkulkit, K. (2010). Chemical modification of chitosan with cationic hyperbranched denderitic polyanidoamine and its antimicrobial activity on cotton fabric, Carbohvd. Polvm.. 80,197-207. 

Sashiwa, H., Norioki, K., Atsuyoshi, N., Einosuke, M., Noboru, Y., and Sei-ichi, A. (2002). Chemical modification of chitosan Synthesis of water-soluble chitosan derivatives by simple acetylation. Biomacromolecules, 3(5), 1126-1128. 

These reactive groups allow for chemical modification of chitosan such as covalent and ionic modifications. 

TABLE 5.1 Selected Chemical Modification of Chitosan Toward Bioactive Intermediates of Chitosan Derivatives for Coupling with Peptides or Proteins... 

C. Jeon, W.H. HoU, Chemical modification of chitosan and equihbrium study for mercury ion removal. Water Res. 37 (2003)4770-4780. 

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