The role of surface charge in the interaction of nanoparticles with model pulmonary surfactants

Abstract

Inhaled nanoparticles traveling through the airways are able to reach the respiratory zone of the lungs. In such an event, the incoming particles first come into contact with the liquid lining the alveolar epithelium, the pulmonary surfactant. The pulmonary surfactant is composed of lipids and proteins that are assembled into large vesicular structures. The question of the nature of the biophysicochemical interaction with the pulmonary surfactant is central to understand how the nanoparticles can cross the air–blood barrier. Here we explore the phase behavior of sub-100 nm particles and surfactant substitutes under controlled conditions. Three types of surfactant mimetics, including the exogenous substitute Curosurf®, a drug administered to infants with respiratory distress syndrome, are tested together with aluminum oxide (Al₂O₃), silicon dioxide (SiO₂) and polymer (latex) nanoparticles. The main result here is the observation of spontaneous nanoparticle–vesicle aggregation induced by coulombic attraction. The role of the surface charges is clearly established. We also evaluate the supported lipid bilayer formation recently predicted and find that in the cases studied these structures do not occur. Pertaining to the aggregate internal structure, fluorescence microscopy shows that the vesicles and particles are intermixed at the nano- to microscale. With particles acting as stickers between vesicles, it is anticipated that the presence of inhaled nanomaterials in the alveolar spaces could significantly modify the interfacial and bulk properties of the pulmonary surfactant and interfere with lung physiology.