Ibuprofen containing mucus-penetrating nanoparticles as therapeutic tool for the treatment of inflammation in Cystic Fibrosis

Conductance regulator protein (CFTR). The airways of CF patients are plugged with mucopurulent secretions containing abundant bacteria and neutrophils, and death results from progressive destruction of the lungs Cystic fibrosis (CF) is a lethal disease triggered by mutations in the gene encoding the CF transmembrane. Ibuprofen was found to significantly reduce this extreme inflammation, but despite the encouraging results obtained, in clinical the anti-inflammatory therapy is rarely practiced because of the poor penetration of drugs through mucus barrier. A novel approach could be allowed by designing particles with mucus-penetrating properties. Generally, particles with size lower than 500 nm and a neutral surface coated by mucus inert materials are able to diffuse through pores generated by the dense fiber mesh of mucus. Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide− 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 ζ potential, and biocompatibility toward human bronchial epithelial cells.