AN IN VITRO HUMAN AIRWAY MODEL FOR RAPID TOXICITY AND FORMULATION SCREENING OF NASAL DRUG DELIVERY SYSTEMS.

INTRODUCTION: Purpose: Nasal delivery of protein and other high molecular weight drugs is an attractive option to injection or oral delivery. However, nasal drug delivery is limited by potential irritation/toxicity issues, difficulties in achieving effective doses and rapidity of clearance from the nasal cavity. These difficulties are best addressed early in formulation development prior to costly animal studies or clinical trials. The goal of the present study was to evaluate the EpiAirway™ organotypic tissue model as a pre-clinical screening tool for nasal drug delivery formulations. SUMMARY AND CONCLUSIONS: • The EpiAirway™ in vitro human airway model is produced from normal human tracheobronchial epithelial cells. • The model reproduces the key histological, ultrastructural and functional features of in vivo nasal and tracheal/bronchial epithelium. • EpiAirway is useful for optimization of respiratory drug delivery formulations using straight-forward protocols for measuring tissue barrier function, viability, and permeability. • EpiAirway has been successfully used to optimize nasal drug formulations. See selected references 1-9 for details of successful applications.

ABCB1 (Pgp), ABCB4, ABCC2 (MRP2), ABCC3, ABCG2 (BCRP), Drug transporter genes, EpiAirway™, Formulation screening, GAPD, Human drug transporters, MT1A, MT1G, MT1H, MT1L, MT1X, MT3, MTT tissue viability, Nasal drug delivery, Permeability, Permeation enhancers, Toxicity, Transepithelial electrical resistance, Transmission electron microscopy

0.25% chitosan, FITC-labeled dextrans