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.

Permeation of Phytochemicals of Selected Psychoactive Medicinal Plants across Excised Sheep Respiratory and Olfactory Epithelial Tissues

“…The permeation results of this ex vivo study are in agreement with the pharmacokinetic results obtained in an in vivo study reported by Hengjumrut et al [46] where the bioavailability of asiaticoside was higher when administered as a single compound, than when it was administered as an extract to rats. Furthermore, the P app values for both the asiaticoside alone and the C. asiatica crude extract across the respiratory tissue were similar to the P app values previously reported for atenolol across respiratory (P app = 0.67 ± 0.11 × 10 −6 cm/s) and olfactory (P app = 2.78 ± 0.36 × 10 −6 cm/s) nasal epithelial tissues, a drug with poor to medium permeability [47].…”

“…vivo study reported by Hengjumrut et al [46] where the bioavailability of asiaticoside was higher when administered as a single compound, than when it was administered as an extract to rats. Furthermore, the Papp values for both the asiaticoside alone and the C. asiatica crude extract across the respiratory tissue were similar to the Papp values previously reported for atenolol across respiratory (Papp = 0.67 ± 0.11 × 10 −6 cm/s) and olfactory (Papp = 2.78 ± 0.36 × 10 −6 cm/s) nasal epithelial tissues, a drug with poor to medium permeability [47]. In general, higher Papp values were obtained for the permeation of asiaticoside in the secretory direction than in the absorptive direction across the excised respiratory and olfactory tissue, which indicated it is subjected to active efflux transport.…”