The mechanism of self-assembled mixed micelles in improving curcumin oral absorption: In vitro and in vivo

Curcumin-loaded self-assembled polymeric micelles (Cur-PMs) were designed to increase oral bioavailability of curcumin and investigate the oral absorption mechanism in vitro and in vivo. The Cur-PMs were spherical nano-size particles 17.82 +/- 0.33 nm in size, with a drug loading of 3.52 +/- 0.18%, and encapsulation efficiency as high as 93.08 +/- 2.23%. The intestinal absorption of Cur-PMs in the duodenum, jejunum, and ileum was 3.09-, 6.48-, and 1.78-fold greater than that of curcumin solution (Cur-Sol) at 0.5 h. The cellular uptake of Cur-PMs in Caco-2 cells was significantly enhanced in comparison with Cur-Sol by caveolae-mediated and clathrin-mediated endocytosis. Moreover, the apparent permeability coefficient (Papp) of Cur-PMs was 3.50-fold higher than that of Cur-Sol in Caco-2 transport studies. The transport mechanism of Cur-PMs into the system circulation was not paracellular transport through opening the tight junctions, but was by energy-dependent, macropinocytic transcytosis and lymphatic transport pathways. Furthermore, the AUC((0-t)) value of Cur-PMs was improved 2.87-fold compared with that of Cur-Sol after oral administration in rats. Therefore, self-assembled polymeric micelles could be a promising vehicle to efficiently improve the oral absorption of curcumin. (C) 2015 Elsevier B.V. All rights reserved.