title: Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency.
abstract: BACKGROUND
  Creatine transporter (CT) deficiency is characterized by mutations in the gene encoding CT, leading to impaired transport of creatine at the cell membrane. Patients with this disease would thus benefit from replenishment of creatine inside the brain cells.
  
  
  OBJECTIVE
  We report a therapeutic strategy based on the use of dodecyl creatine ester incorporated into lipid nanocapsules (LNCs).
  
  
  METHODS
  The dodecyl creatine ester was incorporated in the shells of LNCs using Transcutol(®) (Gattefossé SAS, Saint-Priest, France). The interactions of dodecyl creatine ester encapsulated in LNCs with an in vitro cell-based blood-brain barrier model was studied. The entry of the dodecyl creatine ester encapsulated in LNCs and the conversion of dodecyl creatine ester to creatine in the cells were also studied in the pathological context of CT deficiency.
  
  
  CONCLUSIONS
  We showed that these LNCs can cross the blood-brain barrier and enter brain endothelial cells. In human fibroblasts lacking functional CT, all or part of the dodecyl creatine ester was released from the LNCs and biotransformed to creatine, thus indicating the value of this strategy in this therapeutic context.
authors.affiliation: CEA, Direction des Sciences du Vivant, iBiTec-S, Service de Pharmacologie et d'Immuno Analyse, Equipe Pharmacologie Neurovasculaire, Gif-sur-Yvette, France. aloïse.mabondzo@cea.fr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trotier-Faurion
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.forename: Jérôme
authors.initials: J
authors.lastname: Béjaud
authors.forename: Sophie
authors.initials: S
authors.lastname: Dézard
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Fréderic
authors.initials: F
authors.lastname: Taran
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
authors.forename: Aloïse
authors.initials: A
authors.lastname: Mabondzo
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism; D020739:Brain Diseases, Metabolic, Inborn / Q000378:metabolism*; D003401:Creatine / Q000172:deficiency* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D038901:X-Linked Intellectual Disability / Q000378:metabolism*; D053769:Nanocapsules / Q000737:chemistry*; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D008055:Lipids; D053769:Nanocapsules; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D003401:Creatine
keywords: blood–brain barrier; creatine; creatine transporter deficiency; dodecyl creatine ester; lipid nanocapsule