Modeling and optimization of degree of folate grafted on chitosan and carboxymethyl-chitosan.

Chitosan is a cationic polysaccharide with great properties and so is considered as an attractive biopolymer. However, chitosan shows its antibacterial activity only in acidic environment and this restricts its uses. So water-soluble chitosan derivatives such as carboxymethyl chitosan could be good candidates for such biomedical applications. Modified chitosan with hydrophobic functional groups such as folate (FA) is able to make self-assembled nanoparticles in aqueous media. One of the most important factors affecting the properties of resulting nanoparticles such as size, morphology, amount and efficiency of drug loading and also drug release profile is the amount of FA groups grafted on the chitosan chains. In this study FA modified chitosan and carboxymethyl chitosan have been synthesized using folic acid, -hydroxy succinimide (NHS), , -dicyclohexylcarbodiimide (DCC) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The effect of molecular weight, degree of substitution of carboxymethyl hydrophilic group and primary molar ratio of folic acid to chitosan/carboxymethyl chitosan (CMCS) on degree of substitution of folate functional groups grafted on chitosan chains was modeled using a statistical software package (Design of Expert 8, Trial version). Degree of substitution of grafted folate was measured using UV/Vis spectroscopy. Results show that degree of substitution of CMC and molar ratio of folic acid to chitosan/carboxymethyl chitosan has direct effect on substitution degree of folate and molecular weight has an inverse impact. Also results show that molar ratio of folic acid to chitosan/(CMCS) has the most effect on substitution degree of folate and the proposed model is statistically valid to predict degree of substitution of FA groups on chitosan chains.