Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium

Small molecular weight drugs, peptides, and nanoparticles have previously been shown to localize in the central nervous system after intraneural administration. A basic understanding of direct nose-to-brain drug delivery, particularly for nanoparticles with different physicochemical characteristics, remains unclear. In this study, fluorescence microscopy and stereology were used to track intranasally administered chitosan-coated polystyrene (C-PS) or polysorbate-coated polystyrene (P80-PS) nanoparticles (100 nm or 200 nm in diameter) in olfactory and respiratory nasal epithelia and olfactory bulbs in mice. Chitosan coating caused particles to adhere to the extracellular mucus which could provide useful modality for paracellular drug transport. Nanoparticle transport was exclusively transcellular. None of the nanoparticle formulations showed preference for uptake into olfactory axons over other nasal epithelial cells. Both 100 nm PS and 100 nm P80-PS were observed in olfactory epithelial cells but were absent from the olfactory bulbs; therefore, it is speculated that an optimal nanoparticle diameter for axonal transport is <100 nm in mice.