title: Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death.
abstract: The aim of the present study was to develop and characterize a resveratrol self-emulsifying drug delivery system (Res-SEDDS), and to compare the uptake of resveratrol by bovine aortic endothelial cells (BAECs), and the protection of these cells against hydrogen peroxide-mediated cell death, versus a control resveratrol ethanolic solution. Three Res-SEDDSs were prepared and evaluated. The in vitro self-emulsification properties of these formulations, the droplet size and the zeta potential of the nanoemulsions formed on adding them to water under mild agitation conditions were studied, together with their toxicity on BAECs. An optimal atoxic formulation (20% Miglyol® 812, 70% Montanox® 80, 10% ethanol 96% v/v) was selected and further studied. Pre-incubation of BAECs for 180 min with 25 μM resveratrol in the nanoemulsion obtained from the selected SEDDS significantly increased the membrane and intracellular concentrations of resveratrol (for example, 0.076±0.015 vs. ethanolic solution 0.041±0.016 nmol/mg of protein after 60 min incubation, p<0.05). Resveratrol intracellular localization was confirmed by fluorescence confocal microscopy. Resveratrol nanoemulsion significantly improved the endothelial cell protection from H2O2-induced injury (750, 1000 and 1500 μM H2O2) in comparison with incubation with the control resveratrol ethanolic solution (for example, 55±6% vs. 38±5% viability after 1500 μM H2O2 challenge, p<0.05). In conclusion, formulation of resveratrol as a SEDDS significantly improved its cellular uptake and potentiated its antioxidant properties on BAECs.
authors.affiliation: Laboratoire de Pharmacie Galénique EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire de Pharmacie Galénique, Université de Monastir, Monastir, Tunisia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Amri
authors.affiliation: Laboratoire de Biochimie EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Solenn
authors.initials: S
authors.lastname: Le Clanche
authors.affiliation: Laboratoire de Biochimie EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de Biochimie, Hôpital de Bicêtre AP-HP, Le Kremlin-Bicêtre Cedex, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Thérond
authors.affiliation: Laboratoire de Biochimie EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de Biochimie Métabolique, Groupe hospitalier Pitié-Salpêtrière-Charles-Foix AP-HP, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.affiliation: Laboratoire de Biochimie EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de Biochimie Inter-Hospitalier Cochin-Hôtel-Dieu AP-HP, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Borderie
authors.affiliation: Plateforme Technique de l'IFR71/IMTCE, Imagerie Cellulaire et Moléculaire, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: René
authors.initials: R
authors.lastname: Lai-Kuen
authors.affiliation: Laboratoire de Pharmacie Galénique EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chaumeil
authors.affiliation: Laboratoire de Pharmacie Galénique, Université de Monastir, Monastir, Tunisia.
authors.forename: Souad
authors.initials: S
authors.lastname: Sfar
authors.affiliation: Laboratoire de Pharmacie Galénique EA 4466, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: christine.charrueau@parisdescartes.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Charrueau
mesh_terms: D000818:Animals; D002417:Cattle; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D045703:Emulsifying Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D045703:Emulsifying Agents; D013267:Stilbenes; D000077185:Resveratrol
keywords: Antioxidant; Atheroprotection; Endothelial cells; Nanoemulsion; Oxidative stress-mediated death; Polyphenol