Abstract
Objective
To develop N-(levodopa) chitosan derivatives through click chemistry to study their effect in brain cells.
Significance: This study presents a proof-of-concept that macromolecules such as N-(Levodopa) chitosan derivatives traverse brain cell membranes and induce biomedical functionalities.
Methods
Through click chemistry, we developed N-(levodopa) chitosan derivatives. They were physically and chemically characterized by FT-IR, 1H-NMR, TGA and Dynamic Light Scattering analyses. Solution and nanoparticles of N-(levodopa) chitosan derivatives were tested in primary cell cultures from the postnatal rat olfactory bulb, substantia nigra and corpus callosum. Ca2+ imaging and UPLC experiments were used to investigate if the biomaterial modulated the brain cell physiology.
Results
N-(levodopa) chitosan derivatives induced intracellular Ca2+ responses in primary cell cultures of the rat brain. UPLC experiments indicated that levodopa attached to chitosan was converted into dopamine by brain cells.
Conclusion
The present study shows that N-(levodopa) chitosan may be useful to develop new treatment strategies, which could serve as molecular reservoirs of biomedical drugs to treat degenerative disorders of the nervous system.
GRAPHICAL ABSTRACT
Parkinson’s disease is a neurodegenerative disorder currently leading to several disabilities worldwide. We addressed this, by developing N-(levodopa) chitosan derivatives through green click chemistry to study their capabilities as dopamine precursors for brain cells. Interestingly, we found that in primary cell cultures and brain tissue of the postnatal rat, these chitosan derivatives (solution & nanoparticles) were homogeneously distributed inside of cells’ membranes associated with intracellular Ca2+ responses. Therefore, N-(levodopa) chitosan may be useful as molecular reservoir of drugs to treat degenerative disorders of the nervous system.
Acknowledgments
The authors thank Karla Zavalza Ortega, Bertha Pacheco Moreno, and Monica Villegas Ochoa for their technical assistance.
Disclosure statement
All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.