Treatment of Parkinson's disease: nanostructured sol–gel silica–dopamine reservoirs for controlled drug release in the central nervous system

Abstract

Tessy López1–3, José L Bata-García4, Dulce Esquivel5,2, Emma Ortiz-Islas2, Richard Gonzalez3, Jorge Ascencio6, Patricia Quintana7, Gerko Oskam7, Fernando J Álvarez-Cervera4, Francisco J Heredia-López4, José L Góngora-Alfaro41Departamento de Atención a la Salud, UAM-Xochimilco. Calzada del Hueso, Coyoacán, México; 2Laboratorio de Nanotecnología. Instituto Nacional de Neurología y Neurocirugía MVS, Tlalpan, México; 3Departamento de Química e Ingeniería Biomolecular, Universidad de Tulane, New Orleans, USA; 4Departamento de Neurociencias, Centro de Investigaciones Regionales "Dr Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida, Yucatán; 5Universidad de Guanajuato, Centro de Investigaciones en Química Inorgánica, Noria Alta Guanajuato; 6Instituto de Ciencias Físicas-UNAM, Cuernavaca; 7Departamento de Física Aplicada, CINVESTAV-IPN, Mérida, Yucatán, MéxicoIntroduction: 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 N2 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 m2/g nanostructured silica materials. The stability of dopamine in the silica network was confirmed by infrared and 13C-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.Keywords: Parkinson's disease, silica–dopamine, controlled drug release, central nervous system, reservoirs