Refinement of intranasal delivery in rats: A cadaveric study

The intranasal route enables direct delivery of multiple substances from the nose to the brain, through olfactory and trigeminal pathways, bypassing the blood-brain barrier and avoiding systemic absorption. Despite the potential of this route, the various administration approaches make data reproducibility and interpretation challenging, emphasizing the necessity to establish a consistent methodology. Considering this, the aim of our study was to assess and compare the distribution of two dye volumes (30 µl and 50 µl) in the nasal cavity of rat cadavers. We employed three distinct methods of intranasal delivery: nose drops, by pipette tip, or cannula inserted into the nasal cavity. The results indicated that for both volumes, using the nose drops and the pipette tip methods, the dye dispersion occurred mainly in the vestibule, respiratory and olfactory regions, without reaching the olfactory bulbs. Using the cannula method, the deposition predominantly occurred in the respiratory and olfactory regions, with the dye reaching 66.7% and 100% of the olfactory bulbs, respectively, to low and high volume. Furthermore, the results demonstrated differences between the two volumes, in the pharynx, larynx, trachea, septal window, and incisive papilla, where an increased dye presence was observed with the 50 µl instillation across all three methods. According to our results, the intranasal delivery with a cannula was the most effective method for dye deposition in the olfactory region. However, further studies in live animals will be necessary to determine and refine the administration method that consistently allows specific deposition in the olfactory system.