ABSTRACT
The aim of this study was to encapsulate lapachone (ß-lap) or inclusion complex (ß-lap:HPß-CD) in liposomes and to evaluate their physicochemical characteristics. In addition, the investigation of the main aspects of the interaction between ß-lap and 2-hydroxypropyl-ß-cyclodextrin (HPß-CD), using both experimental and molecular modeling approaches was discussed. Furthermore, the in vitro drug release kinetics was evaluated. First, a phase solubility study of ß-lap in HPß-CD was performed and the ß-lap:HPß-CD was prepared by the freeze-drying technique. A 302-fold increase of solubility was achieved for ß-lap in HPß-CD solution with a constant of association K(1:1) of 961 M(-1) and a complexation efficiency of ß-lap of 0.1538. (1)H NMR, TG, DSC, IR, Raman and SEM indicated a change in the molecular environment of ß-lap in the inclusion complex. Molecular modeling confirms these results suggesting that ß-lap was included in the cavity of HPß-CD, with an intermolecular interaction energy of -23.67 kJ mol(-1). ß-lap:HPß-CD and ß-lap-loaded liposomes presented encapsulation efficiencies of 93% and 97%, respectively. The kinetic rate constants of 183.95±1.82 µg/h and 216.25±2.34 µg/h were calculated for ß-lap and ß-lap:HPß-CD-loaded liposomes, respectively. In conclusion, molecular modeling elucidates the formation of the inclusion complex, stabilized through hydrogen bonds, and the encapsulation of ß-lap and ß-lap:HPß-CD into liposomes could provide an alternative means leading eventually to its use in cancer research.
