Abstract
The interactions with the pulmonary surfactant, the initial biological barrier of respiratory pathway, determine the potential therapeutic applications and toxicological effects of inhaled nanoparticles (NPs). Although much attention has been paid to optimize the physicochemical properties of NPs for improved delivery and targeting, shape effects of the inhaled NPs on their interactions with the pulmonary surfactant are still far from clear. Here, we studied the shape effects of NPs on their penetration abilities and structural disruptions to the dipalmitoyl-phosphatidylcholine (DPPC) monolayer (being model pulmonary surfactant film) using coarse-grained molecular dynamics simulations. It is found that during the inspiration process (i.e., surfactant film expansion), shape effects are negligible. However, during the expiration process (i.e., surfactant film compression), NPs of different shapes show various penetration abilities and degrees of structural disruptions to the DPPC monolayer. We found that rod-like NPs showed the highest degree of penetration and the smallest side-effects to the DPPC monolayer. Our results may provide a useful insight into the design of NPs for respiratory therapeutics.