Tissue-based in vitro and ex vivo models for nasal permeability studies

The nasal epithelium is a complex, highly vascularized and innervated cellular structure that, owing to a high surface area, has been extensively investigated not only for the localized delivery of drugs but also for their systemic delivery. The revelation of a direct pathway to the central nervous system that surpasses the blood-brain barrier has attracted the attention of researchers as a strategy to target relevant drugs to the brain. This pathway is especially efficient for nanostructures of up to 300. nm; its main advantages are simplicity, minimal invasiveness, and patient compliance. At the same time, because of the complexity of the structure, the biological performance of different drug delivery systems is often assessed in vivo employing animal models and techniques that include, for example, microdialysis, a procedure that enables multiple sampling at different time points. However, this approach has drawbacks. The first is that the most common animal models (e.g., rodents) do not necessarily mimic the human nasal mucosa. The second is that at the very early stages of development and when optimization of relevant features of the delivery system is addressed, these approaches are ethically questionable. In this scenario, robust and reliable in vitro and ex vivo models represent a relevant research tool to select the most promising prototypes that will continue to the preclinical stage. This chapter presents a brief overview of the most relevant structural features of the nasal mucosa and then discusses the different proposed models.