Probing the Encapsulation of Fenofibrate with Hydroxypropyl-β-Cyclodextrin Through Molecular Dynamics Simulation and Experimental Characterization
Objective:To investigate the solubilization ability and inclusion mechanism of fenofibrate(FNB)by methyl-β-cyclodextrin(RMβCD).Methods:Phase solubility method in conjunction with molecular dynamics simulation was used to study the dynamic changes of host-guest molecules interaction and binding process in FNB-RMβCD inclusion complex using FNB and RMβCD as model drug and solubilization carrier.Results:The phase solubility curve of FNB and RMβCD was AL type,forming a 1 ∶ 1 molar ratio of inclusion complex.The inclusion stability constant KS at 25,35 and 45℃were 4 969.90,5 833.21 and 7 141.07 L·mol-1,respectively.In molecular docking,the benzene ring part of FNB enters the hydrophobic cavity from the large mouth side of cyclodextrin by intermolecular forces.The RMSD of FNB,RMβCD,and inclusion complexes fluctuated less in 200 ns molecular dynamics simulations.The binding free energy of FNB and RMβCD was(-12.76±1.84)kcal/mol,and the formation of inclusion complexes was a spontaneous process not driven by external forces.The molecular mechanics term was the main contributor to the binding free energy,and the solvation energy had a negative effect on the binding free energy.Conclusion:RMβCD has a good solubilization ability for FNB,and the inclusion behavior is a spontaneous process.
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