Sustained and safe delivery of
dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in
Parkinson's disease (PD), a
neurodegenerative disorder. Therefore, in the present study we designed
neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver
dopamine to the brain. These nanoparticles slowly and constantly released
dopamine, showed reduced clearance of
dopamine in plasma, reduced
quinone adduct formation, and decreased
dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk
dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a
6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic
intravenous administration of DA NPs caused significantly increased levels of
dopamine and its metabolites and reduced
dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats.
Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly,
dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered
dopamine into the brain, reduced
dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats.