Pollen‐Inspired Shell–Core Aerosol Particles Capable of Brownian Motion for Pulmonary Vascularization

Nebulization is the most widely used respiratory delivery technique with non-invasive properties. However, nebulized drugs often fail to function due to the excretion and immune clearance of the respiratory system. In this work, inspired by pollen in nature, novel shell-core aerosol particles (APs) capable of Brownian motion are constructed for respiratory delivery. Drugs-loaded poly(lactic-co-glycolic acid) nanoparticles are prepared by emulsification to form the inner core, and the membranes of macrophages are extracted to form the outer shell. The optimized size and the shell-core structure endow APs with Brownian motion and atomization stability, thus enabling the APs to reach the bronchi and alveoli deeply for effective deposition. Camouflaging the macrophage membranes equips the APs with immune evasion. In vitro experiments prove that deferoxamine (DFO)-loaded APs (DFO@APs) can promote the angiogenesis of human umbilical vein endothelial cells. A hyperoxia-induced bronchopulmonary dysplasia (BPD) model is constructed to validate the efficiency of DFO@APs. In BPD mice, DFO@APs can release DFO in the alveolar interstitium, thus promoting the reconstruction of microvasculature, ultimately inducing lung development for treating BPD. In conclusion, this study develops "pollen"-inspired shell-core aerosol particles capable of Brownian motion, which provides a novel idea and theoretical basis for respiratory administration.