In this study, molecular docking and molecular dynamics simulation were employed to study the interaction between beta cyclodextrin and four isomers of monochlorotriazinyl-β-cyclodextrin with doxorubicin. In order to identify the best conformation of Doxorubicin in the cyclodextrins cavity, molecular docking calculation were performed using AutoDock 4.2 program and for better understanding the interactions, molecular dynamic simulation was employed using GROMACS and charmm36 field force at constant temperature and pressure, in 500 ns. By eva‎luating the lowest binding energy obtained from the molecular docking studies, RMSD, snapshots, distance, SASA, RDF, hydrogen bonds and van der Waals and electrostatic energies from molecular dynamics simulation, it was demonstrated that monochlorotriazinyl-β-cyclodextrin showed the more ability in complexing with Doxorubicin. To validate the theoretical findings, experimental studies were conducted to form inclusion complex between monochlorotriazinyl-β-cyclodextrin and Doxorubicin hydrochloride and then drug loading was done to obtain the optimal laboratory conditions including temperature, time and stoichiometric ratio (1:1) and the encapsulation efficiency was determined 64% then the results were investigated using FT-IR, XRD, SEM, and TGA analyses. Finally, the drug release studies were conducted at 37°C (body temperature) in two environments, first at pH=5.4, simulating cancer cells, second at pH=7.4, representing normal cells. The results showed after 24 hours, 48% of doxorubicin hydrochloride was released in the acidic environment, while 25% was released in the neutral environment. These findings suggest that MCT-β-CD is an appropriate carrier for targeted drug delivery.

محمد ديناري

حسين توكل

حسين فرخ پور , سياوش كاظمي موحد