Dopamine Released from TiO(2) Semicrystalline Lattice Implants Attenuates Motor Symptoms in Rats Treated with 6-Hydroxydopamine

[Image: see text] The motor dysfunction featured by patients aggrieved by Parkinson’s disease (PD) results from the reduction of dopamine (DA) availability in the caudate nucleus (CN). Restituting CN DA levels is therefore essential to ameliorate PD motor deficits. In this regard, nanotechnology may offer solutions to restore CN DA availability. DA, however, can be rapidly oxidized into toxic compounds if made available in situ, unprotected. Then, we tested whether a semicrystalline TiO(2) lattice, implanted into the CN of 6-hydroxydopamine (6-OHDA)-lesioned, hemiparkinsonian rats, was able to release DA during a time window sufficient to attenuate motor symptoms while protecting it from the ongoing oxidation. Accordingly, implanted semicrystalline TiO(2) lattices released incremental amounts of DA into the CN of lesioned rats. Motor symptoms were already attenuated by the 1st month and significantly reduced 2 months after implantation. These effects were specific since TiO(2) lattices alone did not modify motor symptoms in lesioned rats. DA-unloaded or -loaded TiO(2) lattices did not produce obvious symptoms of systemic or neurological toxicity nor significantly increased CN lipid peroxidation in implanted, lesioned rats at the time of sacrifice. Our results thus support that loaded TiO(2) lattices are capable of releasing DA while protecting it from the ongoing oxidation when implanted into the brain. Their implantation does not cause noticeable systemic or local toxicity. On the contrary, they attenuated motor symptoms in hemiparkinsonian rats.