title: Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury.
abstract: There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Alice
authors.initials: A
authors.lastname: Gaudin
authors.affiliation: Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Müge
authors.initials: M
authors.lastname: Yemisci
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Eroglu
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Sinda
authors.initials: S
authors.lastname: Lepetre-Mouelhi
authors.affiliation: Department of Neurosurgery, Ankara Ataturk Research & Education Hospital, 06800 Bilkent Ankara, Turkey.
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Turkoglu
authors.affiliation: Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Buket
authors.initials: B
authors.lastname: Dönmez-Demir
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Seçil
authors.initials: S
authors.lastname: Caban
authors.affiliation: Department of Anatomy, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Mustafa Fevzi
authors.initials: MF
authors.lastname: Sargon
authors.affiliation: CEA Saclay, iBiTecS-S/SCBM, Labex LERMIT, 91191 Gif-sur-Yvette, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Garcia-Argote
authors.affiliation: CEA Saclay, iBiTecS-S/SCBM, Labex LERMIT, 91191 Gif-sur-Yvette, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Pieters
authors.affiliation: CEA Saclay, iBiTecS-S/SCBM, Labex LERMIT, 91191 Gif-sur-Yvette, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Loreau
authors.affiliation: CEA Saclay, iBiTecS-S/SCBM, Labex LERMIT, 91191 Gif-sur-Yvette, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: NanoBioPhotonics, Institut d'Electronique Fondamentale, University of Paris-Sud XI, 91405, Orsay Cedex, France.
authors.forename: Oya
authors.initials: O
authors.lastname: Tagit
authors.affiliation: NanoBioPhotonics, Institut d'Electronique Fondamentale, University of Paris-Sud XI, 91405, Orsay Cedex, France.
authors.forename: Niko
authors.initials: N
authors.lastname: Hildebrandt
authors.affiliation: EA3544, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Dantec
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Julie
authors.initials: J
authors.lastname: Mougin
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Valetti
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Hélène
authors.initials: H
authors.lastname: Chacun
authors.affiliation: Institut d'Innovation Thérapeutique, IFR141 ITFM, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Nicolas
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Karine
authors.initials: K
authors.lastname: Andrieux
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Capan
authors.affiliation: Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Turgay
authors.initials: T
authors.lastname: Dalkara
authors.affiliation: 1] Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, 92296 Châtenay-Malabry, France [2] Labex d'Excellence NanoSaclay.
authors.forename: Patrick
authors.identifier: 0000000179615443
authors.initials: P
authors.lastname: Couvreur