Molecular dynamics simulation of N-octyl-N-quaternized chitosan derivatives as a drug carrier

Abstract

The dynamic amphiphilic behavior of N-octyl-N-quaternized chitosan derivatives in aqueous solution is investigated using molecular dynamics (MD) simulations. It is found that quaternization decreases the intra-chain hydrogen bond formation which leads to reduced rigidity of the chitosan backbone. The effect of octyl substitution is much less pronounced. Analysis of hydrogen bonding reveals the presence of a hydrogen bond within the quaternized glucosamine unit, which causes the distortion of the usual chair conformation. Also, H-bond formation with the solvent water molecules was found to stabilize the intra-chain HO3-O5 hydrogen bond. Additionally, an aqueous solution containing the 10%-N-octyl-50%-N-quaternized chitosan derivative (1O5QCS) and the anti-cancer drug 10-hydroxycamptothecin (10-HCPT) was also investigated using MD simulations. It was found that van der Waals and electrostatic forces have virtually equal contributions to the nonbonded interactions responsible for complexation. Furthermore, H-bond formation between drug and drug carrier contributes to lactone ring stability and subsequent bioavailability.