title: Increased intestinal permeation and modulation of presystemic metabolism of resveratrol formulated into self-emulsifying drug delivery systems.
abstract: Despite various beneficial biological properties, resveratrol lacks therapeutic applications because of poor bioavailability due to variable absorption and extensive metabolism. The present study aims at evaluating the capability of self-emulsifying drug delivery systems (SEDDS) to enhance resveratrol permeation across rat intestine and to modulate its presystemic metabolism. For that purpose, semi-solid (SS) and liquid (L) SEDDS were prepared and dispersed in an aqueous buffer to produce nanoemulsions (NE). The jejunal absorptive transepithelial fluxes (Jms) of resveratrol elicited by these formulations (SS-NE and L-NE) and presystemic metabolization were determined on Ussing chambers. The absorptive fluxes through the intestinal epithelium from the nanoemulsions (Jms=20.5±3.1μgh-1cm-2SS-NE; 28.9±2.9μgh-1cm-2L-NE) were significantly increased compared to an ethanolic control solution (Jms=3.4±0.3μgh-1cm-2, p<0.05). No significant variations of conductance were observed after two hours of contact between the formulations and the mucosa. Simultaneously, the presystemic metabolization pattern was modified in the case of the nanoemulsions compared to the control solution. In conclusion, our data suggests that oil-in-water nanoemulsions prepared from SEDDS dispersions of medium-chain lipids could be promising formulations for enhancing oral delivery of resveratrol.
authors.affiliation: Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France; TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris7, Paris, France. Electronic address: godefroymamadou@wanadoo.fr.
authors.forename: G
authors.initials: G
authors.lastname: Mamadou
authors.affiliation: Unité de Technologies Chimiques et Biologiques pour la Santé UTCBS UMR 8258 CNRS/U1022 INSERM, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Charrueau
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS, Université Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
authors.forename: J
authors.initials: J
authors.lastname: Dairou
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris7, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Limas Nzouzi
authors.affiliation: TransCell-Lab Laboratory, Faculty of Medicine Xavier Bichat, University of Paris Diderot - Paris7, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Eto
authors.affiliation: Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: G
authors.initials: G
authors.lastname: Ponchel
mesh_terms: D000818:Animals; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D045703:Emulsifying Agents; D013267:Stilbenes; D000077185:Resveratrol
keywords: Intestinal absorption; Nanoemulsion; Polyphenol; Resveratrol; Ussing chamber