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.
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