title: Transepithelial Transport of Curcumin in Caco-2 Cells Is significantly Enhanced by Micellar Solubilisation.
abstract: Curcumin, the active constituent of Curcuma longa L. (family Zingiberaceae), has gained increasing interest because of its anti-cancer, anti-inflammatory, anti-diabetic, and anti-rheumatic properties associated with good tolerability and safety up to very high doses of 12 g. Nanoscaled micellar formulations on the base of Tween 80 represent a promising strategy to overcome its low oral bioavailability. We therefore aimed to investigate the uptake and transepithelial transport of native curcumin (CUR) vs. a nanoscaled micellar formulation (Sol-CUR) in a Caco-2 cell model. Sol-CUR afforded a higher flux than CUR (39.23 vs. 4.98 μg min-1cm-2, respectively). This resulted in a higher Pappvalue of 2.11 × 10-6cm/s for Sol-CUR compared to a Pappvalue of 0.56 × 10-6cm/s for CUR. Accordingly a nearly 9.5 fold higher amount of curcumin was detected on the basolateral side at the end of the transport experiments after 180 min with Sol-CUR compared to CUR. The determined 3.8-fold improvement in the permeability of curcumin is in agreement with an up to 185-fold increase in the AUC of curcumin observed in humans following the oral administration of the nanoscaled micellar formulation compared to native curcumin. The present study demonstrates that the enhanced oral bioavailability of micellar curcumin formulations is likely a result of enhanced absorption into and increased transport through small intestinal epithelial cells.
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599, Stuttgart, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599, Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schiborr
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599, Stuttgart, Germany.
authors.forename: Alexa
authors.initials: A
authors.lastname: Kocher
authors.affiliation: Central Laboratory of German Pharmacists, Carl-Mannich-Str. 20, D-65760, Eschborn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Meins
authors.affiliation: AQUANOVA AG, D-64295, Darmstadt, Germany.
authors.forename: Dariush
authors.initials: D
authors.lastname: Behnam
authors.affiliation: Central Laboratory of German Pharmacists, Carl-Mannich-Str. 20, D-65760, Eschborn, Germany.|Institute of Pharmaceutical Chemistry, University of Frankfurt, D-60438, Frankfurt, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.affiliation: Central Laboratory of German Pharmacists, Carl-Mannich-Str. 20, D-65760, Eschborn, Germany. m.tawab@zentrallabor.com.
authors.forename: Mona
authors.initials: M
authors.lastname: Abdel-Tawab
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D003474:Curcumin / Q000493:pharmacokinetics*; D004339:Drug Compounding; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D008823:Micelles; D012995:Solubility
chemical_list: D008823:Micelles; D003474:Curcumin
keywords: Absorption; Bioavailability; Caco-2 cells; Curcumin micelles; Transepithelial transport; Tween 80