Electrosprayed core-shell microspheres co-deliver fibronectin and resveratrol for combined treatment of acute lung injury.

The facile development of advanced formulations capable of scavenging excess reactive oxygen species (ROS) and sustainably inhibiting inflammatory cytokine secretion is imminent for effective treatment of acute lung injury (ALI), but still remains a great challenge. This study presents an innovative core-shell carrier system via electrospray technology, characterized by a shell of poly(lactic acid-co-glycolic acid) (PLGA) and a core consisting of polycaprolactone-polyethylene glycol (PCL-PEG) micelles encapsulating resveratrol (Res), and surface modified with fibronectin (FN). The created drug-loaded core-shell microspheres (for short, RPG@FN) with a size of 1.30 μm, are stable under physiological conditions and specifically target macrophages through the Arg-Gly-Asp peptide sequence of FN. We show that the RPG@FN microspheres can synergistically reduce inflammatory responses through ROS scavenging and macrophage M2 polarization, thus facilitating mitochondrial homeostasis restoration and modulating NF-κB and PI3K/Akt pathways by virtue of the integrated antioxidant and anti-inflammatory properties of FN and Res. In an ALI mouse model, the developed RPG@FN significantly alleviates pulmonary edema and inflammatory cell infiltration, while repairing the inflammatory lung injury. This innovative RPG@FN system fully capitalizes on the therapeutic benefits of Res and FN with improved bioavailability, thus offering a promising option for effective ALI treatment.