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

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 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.

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.

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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

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Acknowledgments

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.

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

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Correspondence to Liu Zhongfa.

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Zhongfa, L., Chiu, M., Wang, J. et al. Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice. Cancer Chemother Pharmacol 69, 679–689 (2012). https://doi.org/10.1007/s00280-011-1749-y

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Keywords

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