N-(levodopa) chitosan derivative based on click chemistry shows biological functionality in brain cells

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 Ca 2+ responses. Therefore, N-(levodopa) chitosan may be useful as molecular reservoir of drugs to treat degenerative disorders of the nervous system. 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. 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. Ca 2+ imaging and UPLC experiments were used to investigate if the biomaterial modulated the brain cell physiology. N-(levodopa) chitosan derivatives induced intracellular Ca 2+ responses in primary cell cultures of the rat brain. UPLC experiments indicated that levodopa attached to chitosan was converted into dopamine by brain cells. 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.