Increasing hydrophobicity of nanoparticles intensifies lung surfactant film inhibition and particle retention

Polymeric nanoparticles (NPs) have had much focus on their ability to penetrate deep pulmonary structures as potential drug carriers. However, research on the toxicological effects of NPs is in its infancy, and interaction mechanisms are largely unknown. Studies have shown that the interactions with pulmonary structures are heavily dependent on the physicochemical properties of the NPs. Here, we studied how hydrophobicity of polymeric NPs affect pulmonary surfactant biophysics in vitro. We investigated a naturally derived lung surfactant, Infasurf, mixed with three polymeric NPs with varying hydrophobicities through the use of a Langmuir trough and atomic force microscopy to probe the intricacies at the air-water interface. In addition, a novel technique, constrained drop surfactometer (CDS), was used to gain insight on how NPs affect surfactant under physiological conditions. We found that the CDS can be used as a sensitive precautionary tool for identifying surfactant inhibition by NPs. Our data suggest that increasing surface hydrophobicity of NPs yields more retention in the surfactant monolayer and a higher degree of surfactant inhibition.