Dexamethasone-loaded H₂O₂-activatable anti-inflammatory nanoparticles for on-demand therapy of inflammatory respiratory diseases

Asthma is a common airway inflammatory disorder, characterized by increased infiltration of leukocytes and bronchoconstriction. Dexamethasone (DEX) has been widely used in the treatment of allergic asthma. However, long-term and frequent use of DEX has side effects. We therefore reasoned that if drug carriers have intrinsic anti-inflammatory and anti-asthmatic activity and synergize with drug payloads, a low dose of DEX could exert sufficient therapeutic effects. In this study, we developed DEX-loaded H₂O₂-activatable boronate maltodextrin (DEX-BM) nanoparticles. DEX-BM nanoparticles released DEX in a H₂O₂-triggered manner and remarkably suppressed the expression of pro-inflammatory cytokines in activated macrophages and lung epithelial cells. In the studies of a murine allergic asthma model, DEX-BM nanoparticles (5 mg/kg) effectively inhibited the inflammatory cell infiltration and airway inflammation than equivalent DEX and BM nanoparticles without noticeable side effects. We anticipate that DEX-BM nanoparticles hold great potential as therapeutic agents for various airway inflammatory diseases.