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 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.

The Radioprotective Effects of Nano-Curcumin Against Genotoxicity Induced by Iodine-131 in Patients with Differentiated Thyroid Carcinoma (DTC) by Micronucleus Assay

“…Dardano et al (2) also showed this increase of MN (about 3 fold) in control groups without any radioprotectors materials. They have proved a significant protective effect of Ginkgo biloba extract (GBE) in patients with Graves' disease and DTC receiving I-131 therapy for their treatments (2,32). The results of the present research also confirm that the administration of curcumin to the patients, at the current dose, was able to prevent the increase of MN about 34.2% compared with the control group.…”

“…Curcumin showed a strong capacity to scavenging intracellular small oxidative molecules such as H 2 O 2 , HO, and ROO. There are no reports of toxicity of curcumin in oral administration (32,33). Curcumin plasma level range was from 29 to 419 ng/mL (33), and 22 to 42 ng/mL after 2 to 6 hours after single dose (32).…”

“…There are no reports of toxicity of curcumin in oral administration (32,33). Curcumin plasma level range was from 29 to 419 ng/mL (33), and 22 to 42 ng/mL after 2 to 6 hours after single dose (32). Because of poor oral bioavailability of curcumin, some new studies focused on the formulation of this natural product in nano-micelles and water soluble to increase the absorption by intestine (32,33).…”

“…Curcumin plasma level range was from 29 to 419 ng/mL (33), and 22 to 42 ng/mL after 2 to 6 hours after single dose (32). Because of poor oral bioavailability of curcumin, some new studies focused on the formulation of this natural product in nano-micelles and water soluble to increase the absorption by intestine (32,33). The administration of nano-curcumin showed the higher serum level of curcumin in blood and soft tissues.…”

Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease

“…The poor transmembrane ability of Cur suspension may account for a limited and unsatisfactory inhibitory efficacy of Cur for IBD in clinical trials, which targeted preferentially intestinal epithelial cells rather than the deep focus (Lahiff & Moss, 2011). As previously reported, PEG could increase the transmembrane capacity of Cur through either chemical conjugation or physical suspension (Zhongfa et al, 2012). On the basis of prior release study, transmembrane Cur could probably exist in both free and conjugated forms.…”