(27b) Effects of Charged Polymeric Nanoparticles On Pulmonary Surfactant Function

Pulmonary surfactant (PS) is vital for maintaining the normal function of the lungs during respiratory maneuvers. This surfactant layer reduces the surface tension of the alveolar fluid, thereby reducing the energy required to inflate the lungs and stabilizing the alveoli to avoid collapse. Disrupted function of the surfactant layer can lead to impaired gas exchange and decreased lung compliance. In vitro studies have shown that certain nanoparticles have the ability to alter surfactant function. However, it remains unclear which physicochemical properties of the particles cause surfactant inhibition. The present study aims to elucidate the effects of nanoparticle charge on the function of two pulmonary surfactant model systems: a monolayer containing the primary lipid of PS, dipalmitoylphosphatidylcholine (DPPC), and a complex surfactant model derived from calf lungs, Infasurf.

Aqueous solutions containing charged nanoparticles (200 nm carboxyl- or amine-modified polystyrene) were aerosolized as droplets onto monolayers of DPPC or Infasurf. The dynamic surface tension of the surfactant films was measured during compression and expansion cycles using a computer-controlled Langmuir trough equipped with a Wilhelmy plate balance. Surfactant microstructure was studied at various surface pressures using fluorescence microscopy, after addition of the fluorescent probe Texas Red-DHPE to the surfactant film. To aid interpretation of the data, particle properties (size, charge and surface elemental composition) were characterized before and after surfactant interaction.

Nanoparticle-induced changes to surfactant function were based on the composition of the surfactant film, particle dose and charge. On the DPPC films, nanoparticles led to a dose dependent increase in the liquid expanded-liquid condensed coexistence region, independent of particle charge. This led to early gelation of lipid condensed domains and, in some cases, a torn monolayer. Nanoparticle aggregation was observed upon interaction with DPPC, but did not induce a change in particle charge. These results suggest a stabilizing effect of charged nanoparticles on DPPC films due to an electrostatic screening effect. This effect reduces electrostatic repulsion between the DPPC head groups, leading to the formation of smaller condensed phases and an excess of liquid lipids during the transition phase.