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Article Dans Une Revue European Journal of Pharmaceutics and Biopharmaceutics Année : 2014

Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death

Résumé

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((R)) 812, 70% Montanox((R)) 80, 10% ethanol 96% v/v) was selected and further studied. Pre-incubation of BAECs for 180 min with 25 mu M 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 mu M H2O2) in comparison with incubation with the control resveratrol ethanolic solution (for example, 55 +/- 6% vs. 38 +/- 5% viability after 1500 mu M 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. (C) 2013 Elsevier B.V. All rights reserved.
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Dates et versions

hal-03292057 , version 1 (20-07-2021)

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Ahmed Amri, Solenn Le Clanche, Patrice Therond, Dominique Bonnefont-Rousselot, Didier Borderie, et al.. Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death. European Journal of Pharmaceutics and Biopharmaceutics, 2014, 86 (3), pp.418-426. ⟨10.1016/j.ejpb.2013.10.015⟩. ⟨hal-03292057⟩
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