Experimental and computational characterization of p-Sulfocalix4arene mediated delivery system for morin hydrate

Calixnarene is a class of macrocyclic compounds and has been investigated to improve the physicochemical properties of water insoluble molecules. In this work, a complex of morin hydrate (MH) drug was prepared using p-sulfocalix4arene (SC4A) as complexing agent to increase its water solubility, dissolution rate and stability. Solvent evaporation methanol was used to prepare the inclusion complex (MH-SC4A) between pure MH and SC4A and analysed by FTIR, NMR, UV, DLS, TEM, and DSC techniques. Concentration-dependent solubility study showed 22 folds enhancement of MH at 8 mM concentration of SC4A. The therapeutic efficacy of MH such as cytotoxicity against A549 cells was increased after complex formation AO/EtBr staining study showed the more apoptosis mediated anticancer activity than native MH. Molecular geometry, stabilizing interactions, release behaviour and full-unwinding pathway of the complex was characterized by the computed Potential of Mean Force (PMF) using extended umbrella sampling. The combined computational and experimental data confirmed that our designed MH-SC4A complex could be utilized as a promising drug delivery carrier for hydrophobic MH.