Original Article

Journal of Inclusion Phenomena and Macrocyclic Chemistry

, Volume 64, Issue 3, pp 215-224

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

  • Mariane C. B. LiraAffiliated withGrupo de Sistema de Liberação Controlada de Medicamentos, Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE)
  • , Milena S. FerrazAffiliated withGrupo de Sistema de Liberação Controlada de Medicamentos, Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE)
  • , Dáfila G. V. C. da SilvaAffiliated withGrupo de Sistema de Liberação Controlada de Medicamentos, Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE)
  • , Maria E. CortesAffiliated withFaculdade de Odontologia, Universidade Federal de Minas Gerais (UFMG)
  • , Karina I. TeixeiraAffiliated withFaculdade de Odontologia, Universidade Federal de Minas Gerais (UFMG)
  • , Nelly P. CaetanoAffiliated withUniversidade Federal de Pernambuco
  • , Ruben D. SinisterraAffiliated withDepartamento de Química, Universidade Federal de Minas Gerais
  • , Gilles PonchelAffiliated withFaculté de Pharmacie, Université Paris-Sud 11, UMR CNRS 8612
  • , Nereide S. Santos-MagalhãesAffiliated withGrupo de Sistema de Liberação Controlada de Medicamentos, Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE) Email author 

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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-cyclodextrin Usnic acid Inclusion drug complex Liposomes Antimicrobial activity