Reconstituted Nasal Epithelium As A Model For Nasal Drug Delivery

This poster presents Reconstituted Nasal Epithelium (RNE) as a superior model for evaluating nasal drug delivery compared to traditional models such as frozen nasal mucosa. Intranasal delivery has advantages like high vascularization and CNS access, but existing ex vivo models fail to maintain vital cellular components (e.g., tight junctions, mucus production). MedPharm developed an RNE model using differentiated primary human nasal epithelial cells, offering a more physiologically relevant system.

The team compared formulation performance in RNE versus frozen mucosa using two formulations, A and B. While frozen mucosa showed large variability and poor discrimination, RNE clearly distinguished between the two, with reduced variability and statistically significant differences in permeation. Further studies with oxycodone and buprenorphine demonstrated that RNE data closely mirrored human clinical trial results, showing strong correlation in permeation and cumulative absorption profiles. For example, oxycodone showed approximately seven-fold higher systemic exposure than buprenorphine in both RNE data and historical clinical data.

The RNE model maintains essential nasal epithelial functions such as tight junction integrity, mucus production, and ciliary activity. This enables better prediction of drug absorption, particularly for active pharmaceutical ingredients and excipients that affect permeability. Additionally, the RNE model offers insights into formulation impact on drug permeation, supporting early-stage drug development.

In conclusion, RNE offers a validated, human-relevant model for nasal drug delivery screening, improving translatability from lab to clinic. Its correlation with clinical outcomes supports its utility in formulation development, regulatory submissions, and expanding nasal drug delivery options.