MD-enhanced DFT investigation of β-cyclodextrin as drug delivery system for Ampyra drug

Cyclodextrins (CDs) have emerged as a promising strategy for the targeted drug delivery process. Herein, the potential of β-cyclodextrin (β-CD) as a drug delivery system for the Ampyra (AMP) drug was extensively investigated. By means of the molecular dynamics (MD) simulation technique, the inclusion process of AMP with β-CD was first examined and consequently subjected to clustering analysis. Upon the obtained five configurations (A↔E) of AMP⋯β-CD complex, extensive density functional theory (DFT) calculations were executed. The favorability of the quested encapsulation process was affirmed by negative adsorption and interaction energies of the selected configurations A↔E affirmed the occurrence of the quested encapsulation process. In particular, configuration A is more energetically preferred compared to other analogs. The insights from SAPT analysis verified the dominant role of electrostatic and dispersion forces in the interactions within the studied configurations A↔E. From QTAIM and NCI analyses, the occurrence and nature of intermolecular interactions within the studied configurations A↔E were illustrated. As per the electronic analysis, the effect of the AMP encapsulation process on the electronic features of β-CD was emphasized. The enhancing impact of the aqueous medium on the studied configurations A↔E was verified by negative adsorption and solvation energies. Moreover, the calculated recovery time values pinpointed the separation potential of AMP from β-CD at the target cell. Overall, the obtained outcomes provided insights into the potential application of β-CD as a drug delivery system, particularly for AMP drug.