Here, the preparation of mucus-penetrating
nanoparticles for pulmonary administration of ibuprofen in
patients with cystic fibrosis is described. A fluorescent
derivative of \u3b1,\u3b2-poly(N-2-hydroxyethyl)-D,L-aspartamide is
synthesized by derivatization with rhodamine, polylactide,
and poly(ethylene glycol), to obtain polyaspartamide 12
polylactide derivatives with different degrees of pegylation.
Starting from these copolymers, fluorescent nanoparticles with
different poly(ethylene glycol) content, empty and loaded with
ibuprofen, showed spherical shape, colloidal size, slightly
negative \u3b6 potential, and biocompatibility toward human bronchial epithelial cells. The high surface poly(ethylene glycol) density
of fluorescent nanoparticles and poly(ethylene glycol) brush-like conformation assumed on their surface, conferred to pegylated
nanoparticles the mucus-penetrating properties, properly demonstrated by assessing their ability to avoid interactions with mucus
components and to penetrate cystic fibrosis artificial mucus. Finally, ibuprofen release profile and uptake capacity within human
bronchial epithelial cells in the presence of cystic fibrosis artificial mucus showed how these mucus-penetrating nanoparticles
could rapidly diffuse through the mucus barrier reaching the mucosal surface, where they could offer a sustained delivery of
ibuprofen at the site of disease