title: Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor.
abstract: The dynamics of the formation of siRNA-lipoplexes coated with hyaluronic acid (HA) and the parameters influencing their supramolecular organization were studied. The insertion of a HA-dioleylphosphatidylethanolamine (DOPE) conjugate in the liposome structure as well as subsequent complexation with siRNA increased the liposome size. Lipoplexes were around 110 nm at high ± charge ratios with a zeta potential around +50 mV and around 230 nm at low ± ratios, with a zeta potential that decreased to negative values, reaching -45 mV. The addition of the conjugate did not compromise siRNA binding to liposomes, although these nucleic acids induced a displacement of part of the HA-DOPE conjugate upon lipoplex formation, as confirmed by capillary electrophoresis. Isothermal titration calorimetry, X-ray diffraction studies, and cryo-TEM microscopy demonstrated that in addition to electrostatic interactions with siRNA a rearrangement of the lipid bilayers takes place, resulting in condensed oligolamellar vesicles. This phenomenon is dependent on the number of siRNA molecules and the degree of modification with HA. Finally, the suitable positioning of HA on the lipoplex surface and its ability to bind specifically to the CD44 receptors in a concentration-dependent manner was demonstrated by surface plasmon resonance analysis.
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CAPES Foundation, Ministry of Education of Brazil, Brasília DF 70040-020, Brazil.
authors.forename: Thais L
authors.initials: TL
authors.lastname: Nascimento
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Noiray
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Claudie
authors.initials: C
authors.lastname: Bourgaux
authors.affiliation: Dipartemento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Facoltà di Farmacia , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
authors.affiliation: Institut Pasteur, Plate-Forme de Microscopie Ultrastructurale, 25-28 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Pehau-Arnaudet
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Taverna
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta" , Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Cosco
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.affiliation: Faculté de Pharmacie, Institut Galien Paris-Sud. Université Paris-Sud , LabEx LERMIT, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.|CNRS, UMR 8612, 5 rue JB Clément, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D001665:Binding Sites; D016503:Drug Delivery Systems; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D018960:Hyaluronan Receptors; D008051:Lipid Bilayers; D034741:RNA, Small Interfering; D006820:Hyaluronic Acid