Research Article published by Elsevier Volume 292, 15 October 2019We report a metadynamics study of toussantine-A with chitosan nanoparticle in dimethyl sulfoxide and water in order to assess the solvent related effects on free energy and interaction stability between the two compounds. We use well-tempered metadynamics to characterize the binding and unbinding processes of toussantine-A from chitosan. The calculated binding free energies support unbinding process deduced from metadynamics simulation. Toussantine-A interacts poorly with chitosan in the presence of dimethyl sulfoxide when compared to water; the dimethyl sulfoxide gives rising a reverse effect on drug binding that favours to the unbinding of toussantine-A.