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The encapsulation of β-lapachone in 2-hydroxypropyl-β-cyclodextrin inclusion complex into liposomes: A physicochemical evaluation and molecular modeling approach

2011; Elsevier BV; Volume: 44; Issue: 3 Linguagem: Inglês

10.1016/j.ejps.2011.08.011

1879-0720

Isabella Macário Ferro Cavalcanti, Elisângela Afonso Moura Mendonça, Mariane Cajubá de Britto Lira Nogueira, Sara B. Honrato, Celso A. Câmara, Rosa Valéria S. Amorim, Josué Mendes Filho, Marcelo Montenegro Rabello, Marcelo Zaldini Hernandes, Alejandro Pedro Ayala, Nereide Stela Santos-Magalhães,

Cancer therapeutics and mechanisms

The aim of this study was to encapsulate lapachone (β-lap) or inclusion complex (β-lap:HPβ-CD) in liposomes and to evaluate their physicochemical characteristics. In addition, the investigation of the main aspects of the interaction between β-lap and 2-hydroxypropyl-β-cyclodextrin (HPβ-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 β-lap in HPβ-CD was performed and the β-lap:HPβ-CD was prepared by the freeze-drying technique. A 302-fold increase of solubility was achieved for β-lap in HPβ-CD solution with a constant of association K1:1 of 961 M−1 and a complexation efficiency of β-lap of 0.1538. 1H NMR, TG, DSC, IR, Raman and SEM indicated a change in the molecular environment of β-lap in the inclusion complex. Molecular modeling confirms these results suggesting that β-lap was included in the cavity of HPβ-CD, with an intermolecular interaction energy of −23.67 kJ mol−1. β-lap:HPβ-CD and β-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 β-lap and β-lap:HPβ-CD-loaded liposomes, respectively. In conclusion, molecular modeling elucidates the formation of the inclusion complex, stabilized through hydrogen bonds, and the encapsulation of β-lap and β-lap:HPβ-CD into liposomes could provide an alternative means leading eventually to its use in cancer research.