1 Département de Chimie, Université de Montréal, Complexe des Sciences, C.P. 6128, Succursale Centre-ville, Montréal, Quebec H3C 3J7, Canada.
2 FRQNT Centre Québécois sur les Matériaux Fonctionnels-Quebec Centre for Advanced Materials, McGill University, 845 Sherbrooke Street West, Montréal, Quebec H3A 0G4, Canada.
3 Department of Chemistry and Biochemistry and Centre for NanoScience Research, Concordia University, 7141 Sherbrooke Street West, Montréal, Quebec H4B 1R6, Canada.

Nanoparticle carriers show promise for drug delivery, including by inhalation, where the first barrier for uptake in the lungs is the monolayer pulmonary surfactant membrane that coats the air/alveoli interface and is critical to breathing. It is imperative to establish the fate of potential nanocarriers and their effects on the biophysical properties of the pulmonary surfactant. To this end, the impact of the nanoparticle surface charge on the lateral organization, thickness, and recompressibility of Langmuir monolayers of model phospholipid-only and phospholipid-protein mixtures was investigated using native and modified forms of nanophytoglycogen, a carbohydrate-based dendritic polymer extracted from corn as monodisperse nanoparticles. We show that the native (quasi-neutral) and anionic nanophytoglycogens have little impact on the phase behavior and film properties. By contrast, cationic nanophytoglycogen alters the film morphology and increases the hysteresis associated with the work of breathing due to its electrostatic interaction with the anionic phospholipids in the model systems. These findings specifically highlight the importance of surface charge as a selection criterion for inhaled nanoformulations.