AN IN VITRO MODEL FOR THE RAPID SCREENING OF POTENTIAL COMPONENTS AND FORMULATIONS FOR NASAL DRUG DELIVERY.

Clinical trials have indicated that nasal delivery of a variety of drugs is both possible and, in some cases, superior to either injections or oral delivery. The two main drawbacks of nasal delivery are the limited maximum dose per spray and the rapidity of clearance from the nasal cavity. These difficulties can best be addressed early in the formulation development. Clinical trials, however, are both costly and time consuming, and are ill suited for screening large numbers of candidate formulations. Initial in vitro screening of drug formulation candidates can provide a rapid, highly effective and low cost alternative to expensive animal and human clinical screens. When choosing an in vitro model it is imperative that the system be robust, reliable, and able to produce consistent, reproducible data. Scientists at SUNY Stony Brook performed studies evaluating MatTek’s EpiAirway™ System as a pre-clinical screening model for nasal drug delivery formulations. The EpiAirway™ System closely resembles human nasal epithelium, both structurally and functionally. The tissue construct consists of normal, non-smoking human-derived tracheal/bronchial epithelial cells (TBE) grown on collagen coated, porous cell culture inserts in serum-free medium to form a multi-layered model that closely resembles the pseudostratified epithelium of the nasal cavity. The constructs have been demonstrated to be highly differentiated in culture, with numerous microvilli and cilia on the apical surface of the cultures as well as tight junctions. An apical air-interface design allows for both the introduction of test articles to a surface much like in vivo nasal mucosa, and measurement of transepithelial permeability and evaluation of trans-epithelial resistance (TER). The range and reproducibility of behavior of quadruplicate samples of EpiAirway tissue constructs was examined across 18 tissue lots. Tissues were evaluated both for structural integrity, by TER, and for viability, by MTT and LDH release. The TER of these EpiAirway model tissues was consistent with normal human airway tissue. The range of responses, as reflected in the variability within quadruplicate sets, is similar to that which would be expected with in vivo subjects. The EpiAirway™ system exhibits a consistent profile of reliability with tissue responses that were remarkably reproducible in samples run on different days, by different technicians, using different tissue lots. The model retained the characteristics expected of normal tissue. While the system described here does not replace in vivo testing, it is a promising pre-clinical tool with great utility as a primary screen for the development of nasal drug delivery vehicles.

Bronchial, Cilia, Drug delivery, EpiAirway, Microvilli, NHBE, Nasal, Nasal drug delivery, Nasal drug formulations, Pre-clinical screening model, TER, Tight junctions, Tracheal

LDH, Lactate dehydrogenase (LDH), SLPI, Secretory leukocyte protease inhibitor (SLPI)