Intermolecular interaction and molecular dynamics study of carboxymethyl Chitosan… Vitamin C molecular complex for understanding encapsulation and kinetics-controlled released mechanism

Abstract

To Application of carboxymethyl chitosan (CMC) as a basic material for drug delivery is based on its solubility in water. Degree of Substitution (DS) of a carboxyl group which bound to the nucleophile _NH2, _OH, or both of chitosan (N_CMC; O_CMC; N,O_CMC) can affect the solubility of CMC in the water. Furthermore, DS of CMC is the potential factor in the complex system of CMC.Vitamin C that affect the encapsulation and controlled release. However, the experiment was still difficult to explain the location of interaction between vitamin C and the substituted carboxyl group of CMC. In this study, the interaction between vitamin C and substituted carboxyl group of CMC on the _NH2, _OH, or both nucleophile have been modeled by in silico approach using molecular docking and dynamics. The results showed that the substituted carboxyl group on the nucleophile _NH2, _OH, or both can affect its binding energy value (liG) with vitamin C, and those data were able to explain the encapsulation process. The binding energy of carboxymethyl chitosan trimer (CMC_3).Vitamin C complex, the substitution of the carboxyl group on the _NH2 nucleophile (N_CMC_3), was -3.36 kcal/mole. This liG was stronger (more stable) than O_CMC_3.Vitamin C complex and N,O_CMC_3.Vitamin C complex. Whereas the binding energy of carboxymethyl chitosan with 5 monomers (CMC_5), the substitution of the carboxyl group on the _OH nucleophile (O_CMC_5), was -3.15 kcal/mole, stronger than N_CMC_5.Vitamin C complex and N,O_CMC_5.Vitamin C complex. The molecular dynamics simulation explained that the stability of the CMC.Vitamin C complexes was affected by the binding energy, and this data was assumed able to explain the kinetics-controlled released Mechanism. So, it can be concluded that the substitution position of carboxyl groups in chitosan and DS of CMC was the important factor of the stability CMC.Vitamin C complexes.