ABSTRACT
Nasal delivery of therapeutic proteins and peptides is an established alternative to the parenteral route. In contrast to preoral delivery, nasal application is less prone to dilution and metabolic degradation typical for the gastrointestinal (GI) tract. Moreover, in light of promising results with nasal immunization, and the recent introduction of a nasal influenza vaccine (Glück et al., 1999), nasal mucosal vaccination may gain in importance. Although bioavailability and immune response in vivo are the gold standards for the assessment of the nasal route, in vitro studies are helpful and important tools. They may be applied to examine principal mucosal permeabilities and pathways, or mechanisms of permeation. Moreover, metabolism and cellular toxicity issues can be addressed. A general review covering the existing nasal in vitro models was previously given by Schmidt et al. (1998a) and forms the major basis for large parts of this chapter. Briefly, cell line cultures from nasal epithelial cells, due to difficulties in forming confluent monolayers, have shown to be impracticable for routine transport studies. In particular, they are unlikely to serve as a complete model for the rather complex nasal epithelium, with its various region-dependent cell types and all its carriers and enzymes. Moreover, cell line cultures often lack the phenotype typical for the nasal epithelium, i.e. a pseudostratified columnar epithelium. Primary cell cultures of human origin are highly differentiated but difficult and costly to cultivate, and allow only limited passaging. Finally, primary cultures cannot reflect the heterogeneous cellular coexistence typical for the nasal mucosa, consisting of ciliated and non-ciliated cells, basal cells, goblet cells etc. By contrast, excised mucosa, as described here in detail, represents the most relevant model available to date for the respiratory nasal epithelium (Figure 14.1).
