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.

Pulmonary surfactant inhibition of nanoparticle uptake by alveolar epithelial cells

“…Cholesterol which is responsible for less-ordered lipid structures in native surfactant is also absent in Curosurf 18 . Despite these differences, using cryo-TEM, we show that the lipid structures such as uni-or, multi-lamellar/vesicular structures with sizes ranging from a few tens of nanometers to about 2 µm are present in Curosurf 26,39 . These images are presented in S7.…”

“…The dispersions included neat silica nanoparticles at µg ml −1 , silica-Curosurf dispersions at X = 2 ( µg ml −1 , µg ml −1 ) and X = 20 ( µg ml −1 , µg ml −1 ), and neat Curosurf at µg ml −1 . We note that X = 2 exposure condition corresponds to the peak of light scattering intensity of dispersions signifying a mixing ratio where the interactions result in largest aggregates 26 . The condition X = 20 is closer to the estimated mixing ratio in the lungs 29 .…”

“…2 e. In this example, it is observed that the nanoparticles come into contact and adhere to the lipid membranes as marked with an arrow on this image. This is resulting from electrostatic interactions between positively charged silica and vesicle membranes: a surface charge density of + 0.62 e nm −2 drives the electrostatic interactions between the nanoparticles and the negative surface potential of surfactant vesicles, about − 54 mV 26 . However in larger interlamellar gaps, nanoparticles are found in proximity but not adherent to the lipids.…”

Effect of Nanoparticles on the Bulk Shear Viscosity of a Lung Surfactant Fluid

“…Cryo-TEM images have also shown that the silica particles can be internalized in the vesicles, potentially reducing the number of effective bonds in the network formation. 47 In conclusion, it is found that above a threshold concentration, the pulmonary surfactant Curosurf® loaded with alumina particles undergoes a rheological transition from a liquid to a soft solid state. These variations in viscosity are important for alveoli whose function is based on the flow properties of the surfactant layer, as they could cause pulmonary diseases.…”

“…1b). The dispersion stability was assessed using dynamic light scattering at pH 5 and 6.4 over extended periods of time (> months) 47 and the hydrodynamic diameters were found to be time independent at 7 = 64 nm, 60 nm and 34 nm, respectively. The surface charge density was determined using the polyelectrolyte assisted charge titration spectrometry at = +7.3e, +0.62e, and -0.31e nm -2 (Table I) Table I: List of nanoparticles and their characteristics.…”