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

Abstract

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.

Direct affinity of dopamine to lipid membranes investigated by Nuclear Magnetic Resonance spectroscopy

“…Our measurements show no appreciable change of λpeak as a function of increasing IPA concentration (data not shown). The average λpeak for all samples was measured around 288 nm, close to the value reported earlier in 1mM concentration of DA/IPA [11]. We note that an absorption in the 200 to 800 nm region most commonly occurs due to a transition of non-bonding valence-shell electron pairs to the π* energy level.…”

Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

“…These results confirmed that TNT/Ti wire can be successfully employed as a suitable drug-releasing platform for local delivery of CNS transmitters such as DOPA and anticancer drugs such as DOXO, to combat brain neurodegenerative disorders and brain tumors with acceptable dosage and predictable release kinetics. 18,32,34,35 Our results demonstrated that the drug release into the local environment during this time was constant, with a value of about 9 µg and 112 µg per day for DOPA and DOXO respectively. By controlling the dimensions of TNT structures (diameter and length), this local concentration can be controlled and tuned to fit the optimal therapeutic window for the treatment of brain cancer or neurodegenerative diseases.…”

“…By controlling the dimensions of TNT structures (diameter and length), this local concentration can be controlled and tuned to fit the optimal therapeutic window for the treatment of brain cancer or neurodegenerative diseases. 4,34,35 The general approach for brain cancer treatments using implantable devices requires a large drug loading and constant release over extended periods (5-6 weeks). To address this problem, we recently introduced several approaches to considerably extend drug release from TNTs prepared on planar surfaces using polymer micelles and polymer coatings (plasma polymers, chitosan, poly[lactic-coglycolic acid]).…”

Degradation of the electrospun silica nanofiber in a biological medium for primary hippocampal neuron – effect of surface modification

“…13 To characterize the surface properties of the surface-modified SNF substrates, SEM, contact angle measurements, and BET isotherm analyses were conducted. The SEM micrographs showed that the fiber diameters of SNF (254±79 nm), SNF-PDL (258±90 nm), and SNF-APTS (231±54 nm) substrates did not change significantly (Figure 2A-C; one-way analysis of variance, P.0.1).…”

“…[5][6][7] Although inorganic-based biomaterials have seen greater success in sensors, adsorbents, and medicines, [8][9][10][11] their applications in tissue engineering have mainly focused on bone tissue engineering, 11,12 utilizing their good mechanical strength and biocompatibility for in vivo implantation, with limited progress in neuronal tissue engineering. 13 In our previous study, 14 we have introduced a novel inorganic neuronal tissue engineering substrate, the chemically modified silica nanofibers (SNFs), which were electrospun to form biomimetic framework of the extracellular matrix and sol-gel…”