Physicochemical investigation of the complexation between γ-cyclodextrin and doxorubicin in solution and in solid state

The importance of Doxorubicin (Dox) as anti-cancer drug is well recognized. Dox side effects are however a major drawback in an efficient medicinal utilization. Cyclodextrin inclusion is an effective approach to enhance drug delivery and stability. In this research host − guest complex formation of Dox cytotoxic drug with gamma-cyclodextrin (γCD) in aqueous solutions and in solid state was investigated by differential scanning calorimetry (DSC), thermogravimetry (TG), Fourier transform infrared spectroscopy (FT-IR) analysis, scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectroscopy, isothermal titration calorimetry (ITC) and pH measurements. The thermodynamic parameters were discussed considering the weak interactions between γCD and Dox molecules. UV-vis and ITC gave comparable results regarding the formation constant and thermodynamic parameters values. The data indicated that the γCD/Dox complex in the aqueous solution is formed in a 1:1 stoichiometry ratio and the binding process of γCD with Dox is exothermic and enthalpy controlled, but entropy driven. The solid state characterization of the γCD/Dox complex indicated the occurrence of complexation by encapsulation of the hydroxyanthraquinonic rings of Dox into γCD cavity and come to support and complete the data resulted from liquid state investigation.