Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers

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Abstract

Background

More and more preclinical studies support the idea that curcumin, a plant-derived natural polyphenol, could be a promising anticancer drug. However, poor bioavailability has limited its efficacy in clinical trials, and plasma curcumin levels remain low despite patients taking gram doses of curcumin.

Methods

This study aimed to evaluate the safety and pharmacokinetics of newly developed nanoparticle curcumin with increased water solubility (named THERACURMIN). Six healthy human volunteers were recruited and received THERACURMIN at a single oral dose of 150 mg. After an interval of 2 weeks, the same subjects then received THERACURMIN at a single dose of 210 mg. Plasma curcumin levels were measured at 0, 1, 2, 4, 6, and 24 h after THERACURMIN intake using high-performance liquid chromatography (HPLC).

Results

One subject reported grade 1 diarrhea after intake of 150 mg THERACURMIN. No other toxicities were observed in this study. C max for THERACURMIN at 150 and 210 mg was 189 ± 48 and 275 ± 67 ng/ml (mean ± SEM), respectively, and the area under the curve for 24 h was estimated to be 2,649 ± 350 and 3,649 ± 430 ng/ml × h (mean ± SEM), respectively. The t 1/2 was estimated to be 9.7 ± 2.1 h for 150 mg and 13.0 ± 3.3 h for 210 mg.

Conclusion

THERACURMIN can safely increase plasma curcumin levels in a dose-dependent manner at least up to 210 mg without saturating the absorption system. To the best of our knowledge, THERACURMIN is the first nanoparticle formulation of curcumin that demonstrates improved bioavailability in human subjects. We believe this compound could be a promising tool when testing the potential anticancer effects of curcumin in clinical trials.

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Acknowledgments

This work was supported by the Grant-in-Aid for Young Scientists (21790661) from the Japan Society for the Promotion of Science and Japanese Research Foundation for Clinical Pharmacology.

Conflict of interest

A. Imaizumi is a consultant to Theravalues Corporation. Y. Otsuka and H. Sasaki are employees of Theravalues Corporation.

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Correspondence to Masashi Kanai.

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Kanai, M., Imaizumi, A., Otsuka, Y. et al. Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother Pharmacol 69, 65–70 (2012). https://doi.org/10.1007/s00280-011-1673-1

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Keywords

  • Curcumin
  • Nanotechnology
  • Bioavailability
  • THERACURMIN