The Path from Nasal Tissue to Nasal Mucosa on Chip Part 2- Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing

Abstract: The nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, due to several protective functions like the mucociliary clearance, this physiological barrier is a difficult obstacle for drug candidates to overcome. For this reason, effective testing procedures are required in the preclinical phase of pharmaceutical development. Based on a recently reported immortalized porcine nasal epithelial cell line, we developed a test platform based on a tissue-compatible microfluidic chip. A biomimetic glass chip equipped with a controlled bidirectional airflow to induce a physiologically relevant wall shear stress on the epithelial cell layer was microfabricated. By developing a membrane transfer technique, the epithelial cell layer could be pre-cultivated in a static holder prior to cultivation in the microfluidic environment. The dynamic cultivation within the chip showed a homogenous distribution of the mucus film on top of the cell layer and a significant increase of cilia formation compared to static cultivation condition. In addition, the recording of the ciliary transport mechanism by micro particle image velocimetry was successful. Using FITC-dextran 4000 as an example, it was shown that this nasal mucosa on a chip is suitable for permeation studies. The obtained permeation coefficient was in the range of values determined by means of other established in vitro and in vivo models. The novel nasal mucosa on chip can in future be automated and used as a substitute for animal testing.