# Neuroprotective Investigation of Chitosan Nanoparticles for Dopamine Delivery
## 1 Introduction  
Parkinson disease (PD) is a neurodegenerative disorder (ND) caused by degeneration of dopaminergic neurons in the substantia nigra [1]. Despite being the second most common neurodegenerative disease and affecting over 1% of the population above 60 years old, there is currently no cure for PD and its pharmacological therapies are based on the oral administration of DA and dopaminergic drugs to reduce the symptoms. Nevertheless, this approach has several drawbacks, such as the short half-life for circulation and rapid degradation rate, and several side effects, such as nausea, hypotension and dyskinesia. Thus, these factors reduce its therapeutic use [2; 3].  
Recently, nanotechnology has been shown to be able to provide valuable tools for potentially diagnosing and treating diseases in many fields of medicine, including NDs [4; 5; 6; 7; 8; 9; 10]. Furthermore, NPs can help to overcome several limitations of traditional drugs by improving their bioavailability and half-life, yielding a sustained release, in addition to allowing specific targeting [11; 12; 13]. Nanoencapsulation can also increase the stability of photosensitive molecules, enhancing their antioxidant activity only once released [14].  
The exploitation of polymeric NPs in nanomedicine has several advantages due to their biocompatibility, biodegradability, ease of preparation and functionalization as well as low costs.  
Chitosan is a natural polymer that has already proven to be a valuable building block for the formulation of NPs as it is able to deliver several drugs, including DA [15; 16; 17]. Furthermore, its utility in delivering drugs for treating neurological diseases has been recognized because of its ability to positively interfere in neurological processes, which occurs by chelating Cu\({}^{2+}\) ions that can produce hydroxyl radicals causing lipid peroxidation [18; 19].  
Currently, administration of DA is the only treatment for PD. However, due to the poor efficiency of this drug in reaching the site of action, relatively high doses must be used to have a therapeutic effect. However, this leads to several undesired side-effects. Thus, to reduce the occurrence of side-effects, the delivery of DA has been attempted in various ways through nanotechnological approaches [5; 15; 17; 20; 21].  
It is well known that oxidative stress plays a fundamental role in the pathophysiology of neurodegenerative diseases, such as PD. Nevertheless, to the best of our knowledge, all the articles published in the literature studied the delivery of DA from a nanotechnological point of view without investigating the mechanism of action or the effect of the drug delivery to the cells. Although the effect of free DA and free chitosan polymers have been individually investigated in detail, the same approach from a nanotechnological point of view is still missing.  
In this research article, we studied the neuroprotective effect of CS NPs in vitro on SH-SYSY cells and we investigated the different influences of the polymeric NPs, the DA and the loaded nanoformulation in generating ROS and their effect from an enzymatic point of view.