Encapsulation of doxorubicin in carboxymethyl-β-cyclodextrin in aqueous medium mediated by pH-modulated electrostatics interactions

The complexation of doxorubicin with the carboxymethyl-β-cyclodextrin in aqueous medium at different pH values and temperatures was investigated, emphasizing the influence of electrostatic interactions in this complexation. The stoichiometry, the binding constants and the ΔH0 and ΔS0 thermodynamic parameters upon inclusion were obtained. The results were compared to those obtained for the doxorubicin complexation with the natural βCD. For this purpose, UV–Vis, steady-state and time-resolved fluorescence spectroscopic techniques were employed, as well as Molecular Mechanics and Molecular Dynamics calculations to determine their preferred structures and the interactions taking place, both when the cyclodextrin was charged and when it was not. Among the spectroscopic techniques mentioned, the fluorescence lifetime of Dox was used to quantitatively study the thermodynamic parameters, since the fluorescence intensity, which is usually employed, was rather less sensitive to this complexation.