title: The encapsulation of β-lapachone in 2-hydroxypropyl-β-cyclodextrin inclusion complex into liposomes: a physicochemical evaluation and molecular modeling approach.
abstract: 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 K(1:1) of 961 M(-1) and a complexation efficiency of β-lap of 0.1538. (1)H 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.
authors: Universidade Federal de Pernambuco (UFPE), Laboratório de Imunopatologia Keizo-Asami, Recife-PE, Brazil.
authors: Isabella M F
authors: IM
authors: Cavalcanti
authors: Elisângela A M
authors: EA
authors: Mendonça
authors: Mariane C B
authors: MC
authors: Lira
authors: Sara B
authors: SB
authors: Honrato
authors: Celso A
authors: CA
authors: Camara
authors: Rosa V S
authors: RV
authors: Amorim
authors: Josué
authors: J
authors: Mendes Filho
authors: Marcelo M
authors: MM
authors: Rabello
authors: Marcelo Z
authors: MZ
authors: Hernandes
authors: Alejandro P
authors: AP
authors: Ayala
authors: Nereide S
authors: NS
authors: Santos-Magalhães
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D004339:Drug Compounding; D005612:Freeze Drying; D008081:Liposomes; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000277:Adjuvants, Pharmaceutic; D008081:Liposomes; D009285:Naphthoquinones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C014638:beta-lapachone