Pulmonary delivery of bioadhesive nanoparticles for ALI improvement and ARDS prevention with a single-dose administration

Acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), is the major cause of intensive care unit death worldwide. ALI/ARDS is a common condition characterized by a storm of potent inflammatory cytokines. Lung delivery of glucocorticoids (GCs) by inhalation is a potential approach for ALI treatment and ARDS prevention; however, its efficacy is limited by the rapid clearance of GCs in lungs. In this study, we developed surface-modified poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with bioadhesive properties for local delivery to the epidermis of lung tissues, which exhibited prolonged release profile of payloads following intratracheal spraying administration. Compared with that of non-adhesive nanoparticles (NNPs), BNPs showed significantly enhanced adhesion and prolonged retention within lung tissues in vivo. Lipopolysaccharide (LPS)-induced ALI mice treated with betamethasone dipropionate (BD)-loaded BNPs showed significantly fewer lung histological alterations and less lung inflammation than those administered free BD or BD-loaded NNPs, indicating the enhanced therapeutic efficacy of BD/BNPs in ALI. In contrast, the features of ARDS were observed in the animal models without any treatments. Our findings demonstrated that pulmonary delivery of BNPs can maintain their same surface structures and continuously form covalent connections with the contacted tissues, emphasizing their potential to improve the therapeutic efficacy in ALI and prevent from ARDS.