Comparative study of cavitands-based nanocapsule as a drug delivery vehicle for an anti-cancer and multiple sclerosis drug—A DFT study

Nanoscale-assisted drug delivery systems give a platform to alter elementary properties associated with drug particles to limit their adverse effects. In this regard, deep benzimidazolone cavitand-based dimeric nanocapsule, which can act as good host for small guest molecules, is considered to be used as drug delivery vehicle. In the current study, we report the benzimidazolone cavitand-based nanocapsules as drug delivery systems for the drugs, i.e. ampyra (AM) and merceptopurine (MP) at M06-2x/6-31G(d,p) level of theory. AM and MP drugs interact with the nanocapsule with the interaction energies of -26.02 kcal mol^-1 and -24.01 kcal mol^-1, respectively. The results of quantum theory of atoms in molecules (QTAIM) and non-covalent index (NCI) analyses divulge that both the drug molecules are stabilized inside nanocapsule via the hydrogen bonding and van der Waals interactions. The transfer of charge is confirmed through electron density difference (EDD) analyses. Moreover, in the case of MP@cap slightly higher transfer of charge (natural bond orbital; NBO) is observed as compared with AM@cap. Furthermore, frontier molecular orbital (FMO) analyses show the higher energy gap reduction in the case of MP@cap as compared with nanocapsule. The FMO results are consistent with the results of interaction energies, NBO and EDD analyses. Additionally, we have employed <i>ab initio</i> molecular dynamics (AIMD) analysis to find the dynamical stability of drug delivery system after drug loading. Molecular docking has been performed for binding kinetics or the enzymatic interactions of the selected drugs. And, pH effect is studied for understanding the off-loading mechanism of the drugs, which clearly shows the decrease in E_int values pointing towards easier offloading. The analyses of values of dipole moment show that nanocapsule will carry MP drug more efficiently to the target site as compared with AM drug molecule. Overall, the results divulge that the benzimidazolone cavitand-based nanocapsule acts as better carrier for an anti-cancer drug molecule as compared with the other drugs.