title: Dermal quercetin smartCrystals®: Formulation development, antioxidant activity and cellular safety.
abstract: Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations.
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
authors.forename: T
authors.initials: T
authors.lastname: Hatahet
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
authors.forename: M
authors.initials: M
authors.lastname: Morille
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Free University of Berlin, Kelchstr. 31, Berlin 12169, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hommoss
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
authors.forename: C
authors.initials: C
authors.lastname: Dorandeu
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Free University of Berlin, Kelchstr. 31, Berlin 12169, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France. Electronic address: sylvie.begu@enscm.fr.
authors.forename: S
authors.initials: S
authors.lastname: Bégu
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002522:Chlorocebus aethiops; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects*; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods; D014709:Vero Cells
chemical_list: D000975:Antioxidants; D011208:Powders; D013535:Suspensions; D011794:Quercetin
keywords: Antioxidative effect; Cellular toxicity; Flavonoids; Hydrogen peroxide induced toxicity; Nanocrystals; Nanosuspensions; Nonionic gel; Quercetin; SmartCrystals®