Cancer Chemotherapy and Pharmacology

, Volume 69, Issue 3, pp 679–689 | Cite as

Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice

  • Liu ZhongfaEmail author
  • Ming Chiu
  • Jiang Wang
  • Wei Chen
  • Winston Yen
  • Patty Fan-Havard
  • Lisa D. Yee
  • Kenneth K. Chan
Original Article



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.


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.


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.


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.


Nano-emulsion curcumin (NEC) Pharmacokinetics Curcuminoids Curcumin metabolites LC–MS/MS 



Polyethylene glycol


Nano-emulsion curcumin


Suspension curcumin




Mobile phase


Liquid chromatography


Tandem mass spectrometric detection


Internal standard


Coefficient of variation


University laboratory animal resources


Extract ion mass chromatograms


Solid disperse



This work was supported by National Institute of Health (NIH) grants [R21 CA135478] (Zhongfa Liu) and Biomedical Mass Spectrometric Laboratory (Kenneth K. Chan and Zhongfa Liu) at The Ohio State University.

Conflict of interest

The contents of this manuscript have been submitted for a patent application.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Liu Zhongfa
    • 1
    • 2
    Email author
  • Ming Chiu
    • 1
  • Jiang Wang
    • 1
  • Wei Chen
    • 1
  • Winston Yen
    • 1
  • Patty Fan-Havard
    • 4
  • Lisa D. Yee
    • 5
  • Kenneth K. Chan
    • 1
    • 2
    • 3
  1. 1.College of PharmacyThe Ohio State UniversityColumbusUSA
  2. 2.Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  3. 3.College of Medicine and Public HealthThe Ohio State UniversityColumbusUSA
  4. 4.School of Pharmacy and Pharmaceutical SciencesThe State University of New YorkAmherstUSA
  5. 5.The Department of SurgeryThe Ohio State UniversityColumbusUSA

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