Using nanoparticles for drug delivery to the lung has shown great promise in treating lung specific and systemic diseases. After inhalation, nanoparticles first deposition on lung fluids. Nanoparticle interactions with these fluids can change the properties of the nanoparticles, thereby altering how they behave in the lungs. The current study focuses on the interactions of nanoparticles and proteins in the conducting airways. Carboxyl modified polystyrene nanoparticles (200 nm) were used as a particle model and were characterized after interaction with proteins in tracheobronchial secretions as a function of time. Albumin, the protein with the highest concentration in upper lungs, was used as a protein model. We observed a reduction in the charge of nanoparticles and a slight increase in nanoparticle size after interaction with albumin solutions, suggesting that the nanoparticle surface is partially covered by albumin.