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

Int J Biol Macromol. 2023 Dec 31;253(Pt 5):127174. doi: 10.1016/j.ijbiomac.2023.127174. Epub 2023 Sep 30.

Abstract

With respect to the Parkinson's disease (PD), herein, we aimed at synthetizing and characterizing two novel macromolecular conjugates where dopamine (DA) was linked to N,O-carboxymethyl chitosan or O-carboxymethyl chitosan, being both conjugates obtained from an organic solvent free synthetic procedure. They were characterized by FT-IR, 1H NMR spectroscopies, whereas thermal analysis (including Differential Scanning Calorimetry and Thermal Gravimetric Analysis) revealed good stability of the two conjugates after exposure at temperatures close to 300 °C. Release studies in simulated nasal fluid elucidated that a faster release occurred since O-carboxymethyl chitosan-DA conjugate maybe due to the less steric hindrance exerted by the polymeric moiety. The CMCS-DA conjugates prepared in aqueous medium may self-assembly to form polymeric micelles and/or may form polymeric nanoparticles. TEM and Photon correlation spectroscopy lent support for polymeric nanoparticle formation. Moreover, such CMCS-DA conjugates showed antioxidant activity, as demonstrated by DPPH radical scavenging assay. Finally, cytocompatibility studies with neuroblastoma SH-SY5Y cells showed no cytotoxicity of both conjugates, whereas their uptake increased from 2.5 to 24 h and demonstrated in 40-66 % of cells.

Keywords: Chitosan (Compound CID: 129662530); Cytotoxicity; Dopamine; Dopamine hydrochloride (Compound CID: 65340); N,O-carboxymethyl chitosan–Dopamine amide conjugate, O-carboxymethyl chitosan–Dopamine amide conjugate.; Polymeric conjugates; Storage stability; Uptake.

MeSH terms

  • Chitosan* / chemistry
  • Dopamine
  • Drug Carriers / chemistry
  • Humans
  • Neuroblastoma*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Drug Carriers
  • Dopamine
  • Chitosan