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Deacetylation of chitin affords chitosan, a polymer, widely studied for its pharmaceutical and nonpharmaceutical applications. The hurdle in comprehending these applications is its limited solubility. Carboxymethylation of chitosan helps to surmount this hurdle with its improved solubility in water. Though there is ample of research related to carboxymethyl chitosan (CMC) the focused review of the topic is unavailable. Hence an attempt is made in this review to cover the recent findings pertaining to synthesis, characterization of CMC and its applications especially in pharmaceutical field. CMC has been synthesized by ways as direct alkylation, reductive alkylation, Michael addition and characterized by FTIR, NMR spectroscopy, and DSC, titrimetry, viscometry, gel permeation chromatography, X-ray diffraction and capillary zone electrophoresis. The carboxymethyl group can be present at O or N or both the atoms of chitosan molecule. The CMC possess modulated physical and biological properties as chelating, sorption, moisture retention, cell functioning antioxidant, antibacterial, antiapoptotic etc. CMC is used in sustained or controlled release drug delivery, pH responsive drug delivery, DNA delivery as permeation enhancer etc. CMC can be further modified with alkylation, acylation, and grafting. Carboxyalkylation of chitosan yield carboxyethyl, carboxybutyl chitosans. These analogues of CMC may be helpful in substantiating the applications of chitosan.

Chitosan, a polymer obtained by deacetylation of chitin is widely studied for its pharmaceutical and nonpharmaceutical applications. Recommendations about uses of this polymer although could not be always realized due to limited solubility. Chitosan, for example, has been extensively evaluated for its mucoadhesive and absorption enhancement properties. The positive charge on the chitosan molecule gained by acidic environment in which it is soluble seems to be important for absorption enhancement. However chitosan is not soluble in medium except below pH 5.6. This limits its use as permeation enhancer in body compartments where pH is high. In this regard there is a need for chitosan derivatives with increased solubility, especially at neutral and basic pH values. Trimethylation of chitosan is an effort in this direction. Despite the abundance of the research related to trimethyl chitosan (TMC), the overview of the topic is not available. Hence an attempt is made in this review to cover the recent findings pertaining to synthesis, characterization and applications of TMC especially in pharmaceutical field. TMC has been synthesized by different ways and characterized by FTIR, NMR, DSC etc. This quaternized derivative of chitosan possesses a positive charge and is soluble over a wide range of pH. TMC, being a derivative of cationic polymer enriched with positive charge shows better mucoadhesive, permeation enhancement, drug delivery and DNA delivery properties. TMC can be further derivitized or grafted for modulating properties as solubility, cytotoxicity or cell recognition ability. Apart from these applications, TMC itself and its derivatives exhibit antimicrobial properties also. Quaternization of chitosan not only with methyl group but higher group as ethyl or along with spacer or quaternization of modified chitosan can be of interest too.

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