Intranasal delivery of platelet cell membrane-cloaked Astragaloside IV loaded biomimetic nanoparticles for enhanced therapeutics in acute lung injury mice.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) frequently occur alongside sepsis, presenting significant challenges and associated mortality rates between 25 % and 40 %. Despite notable advancements in medical treatment, effective pharmacological options for ALI/ARDS remain limited due to rapid systemic clearance and insufficient targeting of lung tissues. To address this issue, we developed nanoparticles loaded with Astragaloside IV (ASIV-NPs) using an emulsification-evaporation method. Network pharmacology revealed 72 shared targets between ASIV and acute pneumonia, with core nodes (AKT1, CASP3, BCL2, IL6) identified through protein interaction analysis. Enrichment studies linked these targets to critical pathways including JAK-STAT signaling and cellular stress response. Molecular docking confirmed ASIV's strong binding affinity (≤-5 kcal/mol) to key proteins governing inflammation and apoptosis. In vitro, PM@ASIV-NPs demonstrated biocompatibility, targeted inflamed macrophages, suppressed pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), and scavenged ROS. In vivo imaging showed precise lung accumulation, while intranasal administration in ALI mice significantly enhanced IL-10, reduced inflammatory markers, and improved survival. The combined pharmacological evidence elucidates ASIV's multimodal mechanism through target-pathway modulation, aligning with its observed therapeutic effects. This biomimetic nanoplatform utilizing platelet membrane camouflage offers a promising strategy for targeted ALI/ARDS treatment, with potential applicability to COVID-19-related pneumonia.