Cancer Chemotherapy and Pharmacology

, Volume 69, Issue 3, pp 679–689

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

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

DOI: 10.1007/s00280-011-1749-y

Cite this article as:
Zhongfa, L., Chiu, M., Wang, J. et al. Cancer Chemother Pharmacol (2012) 69: 679. doi:10.1007/s00280-011-1749-y

Abstract

Purpose

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 AUC0→24h and more than 40-fold increase in the Cmax 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.

Conclusion

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.

Keywords

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

Abbreviations

PEG

Polyethylene glycol

NEC

Nano-emulsion curcumin

SC

Suspension curcumin

PK

Pharmacokinetic

MP

Mobile phase

LC

Liquid chromatography

MS/MS

Tandem mass spectrometric detection

I.S.

Internal standard

CV

Coefficient of variation

ULAR

University laboratory animal resources

XIC

Extract ion mass chromatograms

SD

Solid disperse

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Liu Zhongfa
    • 1
    • 2
  • 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