E. Ortiz-Islas

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

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 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.

Catalytic nanomedicine technology: copper complexes loaded on titania nanomaterials as cytotoxic agents of cancer cell.

The anticancer properties of pure copper (II) acetate and copper (II) acetylacetonate, alone and loaded on functionalized sol-gel titania (TiO2), were determined in four different cancer cell lines (C6, RG2, B16, and U373), using increasing concentrations of these compounds. The copper complexes were loaded onto the TiO2 network during its preparation by the solgel process. Once copper-TiO2 materials were obtained, these were characterized by several physical-chemical techniques. An in vitro copper complex–release test was developed in an aqueous medium at room temperature and monitored by ultraviolet spectroscopy. The toxic effect of the copper complexes, alone and loaded on TiO2, was determined using a cell viability 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, when cancer cells were treated with increasing concentrations (15.75–1000 mg/mL) of these. Characterization studies revealed that the addition of copper complexes to the TiO2 sol-gel network during its preparation, did not generate changes in the molecular structure of the complexes. The surface area, pore volume, and pore diameter were affected by the copper complex additions and by the crystalline phases obtained. The kinetic profiles of both copper complexes released indicated two different stages of release: The first one was governed by first-order kinetics and the second was governed by zero-order kinetics. The cell viability assay revealed a cytotoxic effect of copper complexes, copper-TiO2, and cisplatin in a dose-dependent response for all the cell lines; however, the copper complexes exhibited a better cytotoxic effect than the cisplatin compound. TiO2 alone presented a minor cytotoxicity for C6 and B16 cells; however, it did not cause any toxic effect on the RG2 and U373 cells, which indicates its high biocompatibility with these cells.