title: Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice.
abstract: OBJECTIVE
  Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice.
  
  
  METHODS
  This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC-MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software.
  
  
  RESULTS
  A tenfold increase in the AUC                            (0→24h) and more than 40-fold increase in the C                            (max) in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC.
  
  
  CONCLUSIONS
  This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo.
authors.affiliation: College of Pharmacy, The Ohio State University, Room 152, Riffe Building, 500 W. 12th Avenue, Columbus, OH 43210, USA. liu.550@osu.edu
authors.forename: Liu
authors.initials: L
authors.lastname: Zhongfa
authors.forename: Ming
authors.initials: M
authors.lastname: Chiu
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Winston
authors.initials: W
authors.lastname: Yen
authors.forename: Patty
authors.initials: P
authors.lastname: Fan-Havard
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Yee
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Chan
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004655:Emulsions; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009061:Mouth Mucosa / Q000378:metabolism*; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D053719:Tandem Mass Spectrometry
chemical_list: D004655:Emulsions; D003474:Curcumin