ABSTRACT
Supramolecular interactions between ß-lapachone (ß-lap) and cyclodextrins (CDs) were investigated by isothermal titration calorimetry. The most favorable host: guest interaction was characterized using X-ray powder diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), spectroscopy (FT-IR), spectroscopy (2D ROESY) nuclear magnetic resonance (NMR), and molecular modeling. Phase solubility diagrams showed ß-, HP-ß-, SBE-ß-, γ-, and HP-γ-CDs at 1.5% (w/w) allowed an increase in apparent solubility of ß-lap with enhancement factors of 12.0, 10.1, 11.8, 2.4, and 2.2, respectively. ß-lap has a weak interaction with γ- and HP-γ-CDs and tends to interact more favorably with ß-CD and its derivatives, especially SBE-ß-CD (K = 4160 M-1 ; ΔG = -20.66 kJ·mol-1 ). Thermodynamic analysis suggests a hydrophobic interaction associated with the displacement of water from the cavity of the CD by the ß-lap. In addition, van der Waals forces and hydrogen bonds were responsible for the formation of complexes. Taken together, the results showed intermolecular interactions between ß-lap and SBE-ß-CD, thereby confirming the formation of the inclusion complex. Molecular docking results showed 2 main orientations in which the interaction of benzene moiety at the wider rim of the SBE-ß-CD is the most stable (average docking energy of -7.0 kcal/mol). In conclusion, ß-lap:SBE-ß-CD is proposed as an approach for use in drug delivery systems in cancer research.
