The Use Of Chitosan In Industrial, Biomedical & Pharmaceutical Applications

Chitosan is widely used biopolymer in industrial, biomedical and pharmaceutical applications due to its excellent characteristics like biodegradability, biocompatibility and low toxicity. (Agnihotri SA, et al. 2004) However, chitosan has poor aqueous solubility at pH above than 6 limits its application for its use at physiological conditions. Kotze, A. F et al; 1999. Commercially chitosan is obtained with different molecular weight and degree of deacetylation (DD) depend on the primary amino group present in polymer.(Dutta, P. K., J. Dutta, et al. (2004). N, N, N – trimethyl chitosan (TMC) is partially quaternized, water soluble derivative of chitosan which have permanent positive charge on quaternized amino group. TMC is soluble at neutral and basic environment. TMC which can be used as a permeation enhancer for drugs and it is able to open tight junction allowing better absorption of drugs due to its good solubility in wide range of pH values.(Chandrakantsing V. Pardeshi 2015, Thanou, M etak; 2001). TMC is also used as vehicle for gene transfer and antibacterial agent due to ionic interaction between positively charged molecule and negatively charged cells of bacteria. (Huang, J., etal 2013, Xu, T etal 2013)

TMC was traditionally synthesized by using methyl iodide, formaldehyde, dimethyl sulfate (DMS), as methylating agent in presence of organic solvents like N – methylpyrrolidone (NMP), acetic acid and dimethylformamide (Runarssson 2008, Debritto 2007, domard 1986, Ijintapattanalit 2008). It is found that traditionally followed methods for synthesis of TMC results into various degree of quaternization (DQ), selective N – methylation and reduced chain scission as well as use of environmentally hazardous reagents. Thus, there is an still interest in developing new and greener method to obtain TMC in safely manner with respect to both human and environmental point of view.

Therefore, green chemistry has gain much more attention due to its ability of developing sustainable processes to reduce viz; use of hazardous compounds and minimizing byproducts. Green chemistry involves use of renewable, cheap and biodegradable materials to develop sustainable processes. In recent years, TMC was synthesized by using dimethyl carbonate (DMC) as non – toxic and environment friendly reagent in presence of deep eutectic solvents (Bangde p etal 2016). In this manner, deep eutectic solvents (DESs) are newly employed alternatives for organic solvents because they are generally derived from cheap, biodegradable materials (Paiva A etal 2014). Ternary deep eutectic solvents (TDESs) have some special traits such as wide liquid state range, low volatility, biodegradability, non- flammability which makes them suitable reaction media for biocatalytic process (Smith etal 2014; Zhang QL etal 2012)

We investigated a new approach for methylation of chitosan by using green methylating agent dimethyl carbonate and lipase as biocatalyst. Recently, Meiyan Wu and his coworkers synthesized TMC by using DMC as methylating agent in presence of an ionic liquid. (meiyan wu etal 2017) Further, we have demonstrated the role of lipase enzymes in methylation. We utilized lipase enzyme, which is a promiscuous enzyme, known for its catalytic activity at a broad range of pH,at varying temperatures, and for diverse substrate types. We carried out synthesis of TMC by using lipase as biocatalyst and DMC as methylating agent in presence of TDESs made from choline chloride as hydrogen bond acceptor (HBA). TMC synthesis was carried out by variation in parameters like temperature, amount of enzyme and methylating agent as well as reaction time. Use of ternary deep eutectic solvents for biocatalytic reactions is not reported yet. The key aim of this paper was to optimization of reaction parameters for synthesis of TMC and to characterize the product with various analytical methods.