Inclusion complex of usnic acid with β-cyclodextrin: characterization and nanoencapsulation into liposomes

  • Mariane C. B. Lira
  • Milena S. Ferraz
  • Dáfila G. V. C. da Silva
  • Maria E. Cortes
  • Karina I. Teixeira
  • Nelly P. Caetano
  • Ruben D. Sinisterra
  • Gilles Ponchel
  • Nereide S. Santos-Magalhães
Original Article

DOI: 10.1007/s10847-009-9554-5

Cite this article as:
Lira, M.C.B., Ferraz, M.S., da Silva, D.G.V.C. et al. J Incl Phenom Macrocycl Chem (2009) 64: 215. doi:10.1007/s10847-009-9554-5

Abstract

In this study β-cyclodextrin (β-CD) was used to improve usnic acid (UA) solubility and the inclusion complex (UA:β-CD) was incorporated into liposomes in order to produce a targeted drug delivery system for exploiting the antimycobacterial activity of UA. A phase-solubility assay of UA in β-CD at pH 7.4 was performed. An apparent stability constant of K1:1 = 234.5 M−1 and a complexation efficiency of 0.005 was calculated. In the presence of 16 mM of β-CD the solubility of UA (7.3 μg/mL) increased more than 5-fold. The UA:β-CD complex was prepared using the freeze-drying technique and characterized through infrared and 1HNMR spectroscopy, X-ray diffraction and thermal analyses. The UA:β-CD inclusion complex presented IR spectral modifications when compared with UA and β-CD spectra. 1HNMR spectrum of UA:β-CD inclusion complex showed significant chemical shifts in proton H5 located inside the cavity of β-CD (Δδ = 0.127 ppm), suggesting that phenyl ring moiety of UA would be expected to be included within the β-CD cavity, interacting with the H-5 proton. A change in UA from its crystalline to amorphous form was observed on X-ray, suggesting the formation of a drug inclusion complex. DSC analysis showed the disappearance of the UA fusion peak UA:βCD complex. No differences between the antimicrobial activity of free UA and UA:βCD were found, supporting the hypothesis that the complexation with cyclodextrin did not interfere with drug activity. Liposomes containing UA:βCD were prepared using hydration of a thin lipid film method with subsequent sonication. Formulations of liposomes containing UA:βCD exhibited a drug encapsulation efficiency of 99.5% and remained stable for four months in a suspension form. Interestingly, the encapsulation of UA:βCD into the liposomes resulted in a modulation of in vitro kinetics of release of UA. Indeed, liposomes containing UA:β-CD presented a more prolonged release profile of free usnic acid compared to usnic acid-loaded liposomes.

Keywords

β-cyclodextrinUsnic acidInclusion drug complexLiposomesAntimicrobial activity

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Mariane C. B. Lira
    • 1
  • Milena S. Ferraz
    • 1
  • Dáfila G. V. C. da Silva
    • 1
  • Maria E. Cortes
    • 2
  • Karina I. Teixeira
    • 2
  • Nelly P. Caetano
    • 3
  • Ruben D. Sinisterra
    • 4
  • Gilles Ponchel
    • 5
  • Nereide S. Santos-Magalhães
    • 1
  1. 1.Grupo de Sistema de Liberação Controlada de Medicamentos, Laboratório de Imunopatologia Keizo-Asami (LIKA)Universidade Federal de Pernambuco (UFPE)Recife (UFPE)Brazil
  2. 2.Faculdade de OdontologiaUniversidade Federal de Minas Gerais (UFMG)Belo HorizonteBrazil
  3. 3.Universidade Federal de PernambucoRacifeBrazil
  4. 4.Departamento de QuímicaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  5. 5.Faculté de PharmacieUniversité Paris-Sud 11, UMR CNRS 8612Châtenay-MalabryFrance