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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.

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