Document Detail


Treatment of Parkinson's disease: nanostructured sol-gel silica-dopamine reservoirs for controlled drug release in the central nervous system.
MedLine Citation:
PMID:  21289978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: 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.
CONCLUSION: 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:
Tessy López; José L Bata-García; Dulce Esquivel; Emma Ortiz-Islas; Richard Gonzalez; Jorge Ascencio; Patricia Quintana; Gerko Oskam; Fernando J Alvarez-Cervera; Francisco J Heredia-López; José L Góngora-Alfaro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-16
Journal Detail:
Title:  International journal of nanomedicine     Volume:  6     ISSN:  1178-2013     ISO Abbreviation:  Int J Nanomedicine     Publication Date:  2011  
Date Detail:
Created Date:  2011-02-03     Completed Date:  2011-06-06     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  101263847     Medline TA:  Int J Nanomedicine     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  19-31     Citation Subset:  IM    
Affiliation:
Departamento de Atención a la Salud, UAM-Xochimilco. Calzada del Hueso, Coyoacán, México. tessy3@prodigy.net.mx
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Chemistry*
Delayed-Action Preparations
Disease Models, Animal
Dopamine / administration & dosage*,  chemistry,  pharmacokinetics
Drug Implants
Histocytochemistry
Kinetics
Male
Microscopy, Electron, Transmission
Nanostructures / administration & dosage*,  chemistry,  ultrastructure
Nuclear Magnetic Resonance, Biomolecular
Parkinson Disease / drug therapy*,  metabolism,  pathology
Porosity
Rats
Rats, Wistar
Spectroscopy, Fourier Transform Infrared
Substantia Nigra / drug effects,  metabolism,  pathology
X-Ray Diffraction
Chemical
Reg. No./Substance:
0/Delayed-Action Preparations; 0/Drug Implants
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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