(131h) Development of a More Physiologically-Relevant Mucus Mimetic of the Upper Respiratory Tract

The surfaces of the upper respiratory tract (URT) are coated with mucosal fluids that have a gel network structure which imparts viscoelastic properties to the fluid. Surfactant material tightly controls the surface tension of the mucosal air-fluid interface. Significant limitations in the study of these fluids have been the inaccessibility of native respiratory fluids and the lack of a model of respiratory mucus which incorporates both the fluid bulk and surface properties. Therefore, the objective of this research was to develop a more physiologically-relevant in-vitro mimetic of lung mucus which simulates the physicochemical properties of native lung mucus. Toward this goal, mimetics were developed containing mucins, protein, and various ions at concentrations similar to that found in lung. Various concentrations of gluteraldehyde were used to induce crosslinking in the mimetic and to match the bulk viscoelasticity of the mimetics to that of normal and diseased native mucus states. Surfactants (dipalmitoylphosphatidylcholine (DPPC) or an extract of natural surfactant from calf lungs (Infasurf®; Ony, Inc.)) were spread onto the mimetic surfaces to reduce the surface tension to ~30 mN/m. The adsorption of surfactants at the air-mucus interface resulted in major differences in surface tensiometry, surface rheology and surface structure compared to the air-water interface. Further study of these mimetics will aid our understanding of surfactant function and structure on the viscoelastic gel network in the upper respiratory tract. We are now utilizing these mimetics to study nanoparticle transport within the mucosal fluids and the formation of aerosols from the lung fluid surfaces.