Carboxymethyl chitosan dopamine conjugates: Synthesis and evaluation for intranasal anti Parkinson therapy

With respect to the Parkinson's disease (PD), herein, we aimed at synthetizing and characterizing two novelmacromolecular conjugates where dopamine (DA) was linked to N,O-carboxymethyl chitosan or O-carbox-ymethyl chitosan, being both conjugates obtained from an organic solvent free synthetic procedure. They werecharacterized by FT-IR, 1H NMR spectroscopies, whereas thermal analysis (including Differential ScanningCalorimetry and Thermal Gravimetric Analysis) revealed good stability of the two conjugates after exposure attemperatures close to 300 o C. Release studies in simulated nasal fluid elucidated that a faster release occurredsince O-carboxymethyl chitosan-DA conjugate maybe due to the less steric hindrance exerted by the polymericmoiety. The CMCS-DA conjugates prepared in aqueous medium may self-assembly to form polymeric micellesand/or may form polymeric nanoparticles. TEM and Photon correlation spectroscopy lent support for polymericnanoparticle formation. Moreover, such CMCS-DA conjugates showed antioxidant activity, as demonstrated byDPPH radical scavenging assay. Finally, cytocompatibility studies with neuroblastoma SH-SY5Y cells showed nocytotoxicity of both conjugates, whereas their uptake increased from 2.5 to 24 h and demonstrated in 40-66 % ofcells.