Redox-sensitive disulfide-bridged self-assembled nanoparticles of dexamethasone with high drug loading for acute lung injury therapy

Acute lung injury (ALI) arises from an excessive inflammatory response, usually progressing to acute respiratory distress syndrome (ARDS) if not promptly addressed. There is currently a limited array of effective treatments available for ALI. In this study, we developed disulfide bond-bridged prodrug self-assembled nanoparticles (referred to as DSSS NPs). These nanoparticles were consisted of Dexamethasone (Dex) and stearic acid (SA), and were designed to target and treat ALI. DSSS NPs demonstrated a substantial drug loading capacity with 37.75 % of Dex, which is much higher than conventional nanomedicines (usually < 10 %). Moreover, they exhibited the potential to specifically target injured lung tissue and inflammatory microenvironment-responsive release drugs. Consequently, DSSS NPs reduced significantly the levels of pro-inflammatory cytokines and tissue damage in mice with ALI induced by lipopolysaccharide (LPS). Overall, DSSS NPs offer a promising strategy for treatment of acute lung injury.