Utilizing chitosan nanoparticles for the delivery of biologics to the brain via intranasal route

Due to its selective permeability, the blood-brain-barrier presents a major hurdle in brain targeted drug delivery, especially for macromolecules such as proteins or nucleic acids. Nose-to-brain delivery offers a promising opportunity for drug delivery via the olfactory and trigeminal pathway resulting in effective concentrations in the brain tissue and central nervous system when compared to systemic delivery. In this study, polymeric nanoparticles constituted of chitosan, which were further chemically modified and decorated with transferrin as targeting ligand, were utilized to examine the nose-to-brain delivery of proteins. The synthetized chitosan nanoparticles and transferrin decorated chitosan nanoparticles were evaluated for their physicochemical characteristics, release kinetics, cellular uptake and permeability through an epithelial cell layer. The ability of the nanosystem to reach the central nervous system after intranasal administration was assessed using fluorescently labeled nanoparticles containing the model protein β-galactosidase. The results suggest that chitosan nanoparticles can be used for successful delivery of intact proteins to the brain.