title: An optimized molecular inclusion complex of diferuloylmethane: enhanced physical properties and biological activity.
abstract: OBJECTIVE
  The purpose of this study was to explore and evaluate the enhanced physical properties and biological activity of a molecular inclusion complex (MICDH) comprising diferuloylmethane (DFM) and hydroxypropyl-β-cyclodextrin.
  
  
  METHODS
  The preparation conditions of MICDH were optimized using an orthogonal experimental design. The solubility, in vitro release and model fitting, microscopic morphology, molecular structure simulation, anti-lung cancer activity, and action mechanism of MICDH were evaluated.
  
  
  RESULTS
  The solubility of DFM was improved 4400-fold upon complexation with hydroxypropyl-β-cyclodextrin. The release rate of DFM was significantly higher from MICDH than from free DFM. MICDH exhibited higher antitumor activity against human lung adenocarcinoma A549 cells than free DFM. More cells were arrested in the S/G2 phase of the cell cycle or were induced to undergo apoptosis when treated with MICDH than when treated with free DFM. Furthermore, increased reactive oxygen species and intracellular calcium ion levels and decreased mitochondrial membrane potential were observed in cells treated with MICDH.
  
  
  CONCLUSIONS
  MICDH markedly improved the physical properties and antitumor activity of DFM. MICDH may prove to be a preferred alternative to free DFM as a formulation for DFM delivery in lung cancer treatment.
authors.affiliation: Department of Thoracic Surgery, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Qunyou
authors.initials: Q
authors.lastname: Tan
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jianyong
authors.initials: J
authors.lastname: Wu
authors.forename: Hu
authors.initials: H
authors.lastname: Mei
authors.forename: Chunjing
authors.initials: C
authors.lastname: Zhao
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003474:Curcumin
keywords: action mechanism; antitumor activity; biological properties; hydroxypropyl-β-cyclodextrin