An Ex vivo Investigation on Drug Permeability of Sheep Nasal Epithelial Tissue Membranes from the Respiratory and Olfactory Regions

Abstract

Background: Besides systemic drug delivery, the intranasal route of administration has shown potential for direct nose-to-brain drug delivery, which has gained popularity because it bypasses the blood-brain barrier. Objective: The region in the nose from which the epithelial tissue membrane is excised to conduct ex vivo permeation studies for nasal drug delivery studies may be of importance, but the permeability of the epithelium from the different nasal regions has not yet been investigated in the sheep model. Method: The permeation of five selected model compounds (i.e., atenolol, caffeine, Rhodamine 123, FITC-dextran, and Lucifer Yellow) was measured across epithelial tissues that were excised from two different areas of the sheep nasal cavity, namely the ventral nasal concha (representing respiratory epithelium) and the ethmoid nasal concha (representing olfactory epithelium). Results: Although the selected compounds' permeation was generally slightly higher across the olfactory epithelial tissues than across the respiratory epithelial tissues, it was not statistically significant except in the case of atenolol. Conclusion: The presence of olfactory nerves and supporting cells and the gaps between them in the olfactory epithelial tissues may have contributed to the higher permeation of atenolol, but this needs to be further investigated to elucidate the precise mechanism.