The Impact of Lipid Corona on Rifampicin Intramacrophagic Transport Using Inhaled Solid Lipid Nanoparticles Surface-Decorated with a Mannosylated Surfactant

The mimicking of physiological conditions is crucial for the success of accurate in vitro
studies. For inhaled nanoparticles, which are designed for being deposited on alveolar epithelium
and taken up by macrophages, it is relevant to investigate the interactions with pulmonary
surfactant lining alveoli. As a matter of fact, the formation of a lipid corona layer around the
nanoparticles could modulate the cell internalization and the fate of the transported drugs. Based
on this concept, the present research focused on the interactions between pulmonary surfactant and
Solid Lipid Nanoparticle assemblies (SLNas), loaded with rifampicin, an anti-tuberculosis drug.
SLNas were functionalized with a synthesized mannosylated surfactant, both alone and in a blend
with sodium taurocholate, to achieve an active targeting to mannose receptors present on alveolar
macrophages (AM). Physico-chemical properties of the mannosylated SLNas satisfied the
requirements relative to suitable respirability, drug payload, and AM active targeting. Our studies
have shown that a lipid corona is formed around SLNas in the presence of Curosurf, a commercial
substitute of the natural pulmonary surfactant. The lipid corona promoted an additional resistance
to the drug diffusion for SLNas functionalized with the mannosylated surfactant and this improved
drug retention within SLNas before AM phagocytosis takes place. Moreover, lipid corona formation
did not modify the role of nanoparticle mannosylation towards the specific receptors on MH-S cell
membrane.