Lung-specific sulfonium lipid nanoparticle formulation of dexamethasone suppresses endotoxin-induced lung inflammation.

Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of acute respiratory failure arising from the same underlying pathophysiological processes and are associated with substantial morbidity and mortality worldwide. Although corticosteroids such as Dexamethasone are commonly administered to patients with moderate-to-severe ARDS, their clinical benefit remains controversial, and systemic administration is often associated with significant adverse effects. Methods: We developed a targeting ligand-free, sulfonium lipid nanoparticle (sLNP)-based drug delivery system, Dex/DOSEH, for intravenous lung-targeted delivery of dexamethasone. Results: In a lipopolysaccharide (LPS)-induced murine ALI model, treatment with Dex/DOSEH formulation significantly reduced proinflammatory cytokine production, decreased immune cell infiltration, preserved capillary-alveolar barrier integrity, and attenuated histopathological lung injury compared with controls. Discussion: Our findings demonstrate that Dex/DOSEH drug formulation enables effective lung-targeted delivery of dexamethasone and achieves robust anti-inflammatory therapeutic efficacy in ALI. This platform represents a promising therapeutic strategy for the treatment of ALI/ARDS.