Nose-to-brain delivery: A comparative study between carboxymethyl chitosan based conjugates of dopamine

Herein, the synthesis of a novel polymeric conjugate N,O-CMCS-Dopamine (DA) based on an amide linkage is reported. The performances of this conjugate were compared with those of an analogous N,O-CMCS-DA ester conjugate previously studied (Cassano et al., 2020) to gain insight into their potential utility for Parkinson's disease treatment. The new amide conjugate was synthesized by standard carbodiimide coupling procedure and characterized by FT-IR, H-1 NMR spectroscopies and thermal analysis (Differential Scanning Calorimetry). In vitro mucoadhesive studies in simulated nasal fluid (SNF) evidenced high adhesive effect of both ester and amide conjugates. Results demonstrated that the amide conjugate exerted an important role to prevent DA spontaneous autoxidation both under stressed conditions and physiological mimicking ones. MTT test indicated cyto-compatibility of the amide conjugate with Olfactory Ensheating Cells (OECs), which were shown by cytofluorimetry to internalize efficiently the conjugate. Overall, among the two conjugates herein studied, the N,O-CMCS-DA amide conjugate seems a promising candidate for improving the delivery of DA by nose-to-brain administration.

Automated summary

The synthesis and characterization of a novel N,O-CMCS-Dopamine (DA) amide conjugate was reported, showing its potential utility for Parkinson's disease treatment compared to an analogous N,O-CMCS-DA ester conjugate. The amide conjugate played an important role in preventing DA spontaneous autoxidation, and demonstrated cyto-compatibility with Olfactory Ensheating Cells (OECs) for efficient internalization. Overall, the N,O-CMCS-DA amide conjugate appears to be a promising candidate for improving DA delivery via nose-to-brain administration.