(537a) Effects of Polymeric Nanoparticles On Lung Surfactant Function

The pulmonary surfactant is a complex mixture of lipids and proteins which covers the entire alveolar (gas exchange) region of the lungs. The main role of this surfactant layer is to reduce the surface tension of the lung fluids, thereby stabilizing the alveoli from collapse during exhalation. Changes to the surface tension of this fluid can increase the work required for breathing, potentially leading to respiratory distress, and can impair gas exchange in the lung. In recent studies, soot and metal nanoparticles have been shown to adsorb pulmonary surfactant components onto their surfaces, thus leading to lung surfactant dysfunction. In the present study, the effects of polymeric particles on surfactant function have been investigated.

Dipalmitoylphosphatidylcholine (DPPC), the primary lipid component of pulmonary surfactant, was spread on an aqueous subphase from a chloroform solution. Varying concentrations of 200 nm polystyrene nanoparticles, with either a negative or positive charge, were injected into the subphase. At various time points after particle injection, the surface tension of the surfactant film was measured during compression and expansion cycles (to simulate breathing) using a computer controlled Wilhelmy film balance with a platinum plate (Minitrough System 4, KSV Ltd.). Surface pressure versus surface area isotherms were generated at 25 and 37°C. Surfactant microstructure was studied at different surface pressures using fluorescent microscopy.

We observed a slight increase in maximum surface pressure of the isotherm after the addition of carboxyl nanoparticles. However, particle addition led to a decrease in the hysteresis area of the isotherm. Positively charged, amine modified nanoparticles were added to the surface to study the effect of surface charge on surfactant function. These particles showed a decrease in the maximum surface pressure of the isotherm. These results suggest that the negatively-charged particles had a stabilizing effect on the surfactant films, while the positively-charged particles caused surfactant dysfunction. Studies at different particle concentrations and at 37°C showed that particle-surfactant interactions are both temperature- and dose-dependent.