title: Non-inclusion complexes between riboflavin and cyclodextrins.
abstract: OBJECTIVE
  To investigate the molecular interaction between β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) and riboflavin (RF), and to test the anticancer potential of these formulations.
  
  
  METHODS
  The physicochemical characterization of the association between RF and CDs was performed by UV-vis absorption, fluorescence, differential scanning calorimetry and NMR techniques. Molecular dynamics simulation was used to shed light on the mechanism of interaction of RF and CDs. Additionally, in-vitro cell culture tests were performed to evaluate the cytotoxicity of the RF-CD complexes against prostate cancer cells.
  
  
  RESULTS
  Neither βCD nor HPβCD led to substantial changes in the physicochemical properties of RF (with the exception of solubility). Additionally, rotating frame Overhauser effect spectroscopy experiments detected no spatial correlations between hydrogens from the internal cavity of CDs and RF, while molecular dynamics simulations revealed 'out-of-ring' RF-CD interactions. Notwithstanding, both RF-βCD and RF-HPβCD complexes were cytotoxic to PC3 prostate cancer cells.
  
  
  CONCLUSIONS
  The interaction between RF and either βCD or HPβCD, at low concentrations, seems to be made through hydrogen bonding between the flavonoid and the external rim of both CDs. Regardless of the mechanism of complexation, our findings indicate that RF-CD complexes significantly increase RF solubility and potentiate its antitumour effect.
authors.affiliation: Department of Biochemistry, Institute of Biology, State University of Campinas-Unicamp, Campinas, Brazil.
authors.forename: Marcelo Bispo
authors.initials: MB
authors.lastname: de Jesus
authors.forename: Leonardo Fernandes
authors.initials: LF
authors.lastname: Fraceto
authors.forename: Maria Florencia
authors.initials: MF
authors.lastname: Martini
authors.forename: Monica
authors.initials: M
authors.lastname: Pickholz
authors.forename: Carmen Veríssima
authors.initials: CV
authors.lastname: Ferreira
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012256:Riboflavin / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D012256:Riboflavin