Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers
- 1.8k Downloads
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.
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).
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.
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.
KeywordsCurcumin Nanotechnology Bioavailability THERACURMIN
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.
- 2.Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB (2010) Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol 79:330–338PubMedCrossRefGoogle Scholar
- 3.Ankola DD, Viswanad B, Bhardwaj V, Ramarao P, Kumar MN (2007) Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy? Eur J Pharm Biopharm 67:361–369PubMedCrossRefGoogle Scholar
- 7.Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900PubMedGoogle Scholar
- 10.Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ (2005) Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 14:120–125PubMedGoogle Scholar
- 14.Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, Nishimura T, Mori Y, Masui T, Kawaguchi Y, Yanagihara K, Yazumi S, Chiba T, Guha S, Aggarwal BB (2010) A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol [Epub ahead of print]Google Scholar
- 23.Ohori H, Yamakoshi H, Tomizawa M, Shibuya M, Kakudo Y, Takahashi A, Takahashi S, Kato S, Suzuki T, Ishioka C, Iwabuchi Y, Shibata H (2006) Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer. Mol Cancer Ther 5:2563–2571PubMedCrossRefGoogle Scholar
- 25.Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T (2011) Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull (in press)Google Scholar
- 27.Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ, Steward WP (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10:6847–6854PubMedCrossRefGoogle Scholar