title: The mechanism of self-assembled mixed micelles in improving curcumin oral absorption: In vitro and in vivo.
abstract: 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±0.33nm 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 0.5h. 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.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, PR China.
authors.forename: Wenzhuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: pengfeitu@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002853:Chromatography, Liquid; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004705:Endocytosis; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008823:Micelles; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D008823:Micelles; D003474:Curcumin
keywords: Curcumin; Endocytosis; Intestinal absorption; Oral bioavailability; Polymeric micelles; Transcytosis