title: Treatment of Parkinson's disease: nanostructured sol-gel silica-dopamine reservoirs for controlled drug release in the central nervous system.
abstract: BACKGROUND
  We have evaluated the use of silica-dopamine reservoirs synthesized by the sol-gel approach with the aim of using them in the treatment of Parkinson's disease, specifically as a device for the controlled release of dopamine in the striatum. Theoretical calculations illustrate that dopamine is expected to assume a planar structure and exhibit weak interactions with the silica surface.
  
  
  METHODS
  Several samples were prepared by varying the wt% of dopamine added during the hydrolysis of tetraethyl orthosilicate. The silica-dopamine reservoirs were characterized by N(2) adsorption, scanning and transmission electron microscopy, and Fourier transform infrared spectroscopy. The in vitro release profiles were determined using ultraviolet visible absorbance spectroscopy. The textural analyses showed a maximum value for the surface area of 620 m(2)/g nanostructured silica materials. The stability of dopamine in the silica network was confirmed by infrared and (13)C-nuclear magnetic resonance spectroscopy. The reservoirs were evaluated by means of apomorphine-induced rotation behavior in hemiparkisonian rats.
  
  
  RESULTS
  The in vitro dopamine delivery profiles indicate two regimes of release, a fast and sustained dopamine delivery was observed up to 24 hours, and after this time the rate of delivery became constant. Histologic analysis of formalin-fixed brains performed 24-32 weeks after reservoir implantation revealed that silica-dopamine implants had a reddish-brown color, suggesting the presence of oxidized dopamine, likely caused by the fixation procedure, while implants without dopamine were always translucent.
  
  
  CONCLUSIONS
  The major finding of the study was that intrastriatal silica-dopamine implants reversed the rotational asymmetry induced by apomorphine, a dopamine agonist, in hemiparkinsonian rats. No dyskinesias or other motor abnormalities were observed in animals implanted with silica or silica-dopamine.
authors.affiliation: Departamento de Atención a la Salud, UAM-Xochimilco. Calzada del Hueso, Coyoacán, México. tessy3@prodigy.net.mx
authors.forename: Tessy
authors.initials: T
authors.lastname: López
authors.forename: José L
authors.initials: JL
authors.lastname: Bata-García
authors.forename: Dulce
authors.initials: D
authors.lastname: Esquivel
authors.forename: Emma
authors.initials: E
authors.lastname: Ortiz-Islas
authors.forename: Richard
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Jorge
authors.initials: J
authors.lastname: Ascencio
authors.forename: Patricia
authors.initials: P
authors.lastname: Quintana
authors.forename: Gerko
authors.initials: G
authors.lastname: Oskam
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Alvarez-Cervera
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Heredia-López
authors.forename: José L
authors.initials: JL
authors.lastname: Góngora-Alfaro
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004343:Drug Implants; D006651:Histocytochemistry; D007700:Kinetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D004298:Dopamine