Inhalable Nano-Astaxanthin for Radiation-Induced Lung Injury via Enhanced Lung Retention and Inflammation Suppression

Radiation-induced lung injury (RILI) is a major complication of clinical radiotherapy, characterized by oxidative stress, inflammation, and progressive fibrosis. Astaxanthin (ASX), a potent natural antioxidant, can effectively scavenge radiation-induced reactive oxygen species; however, its therapeutic potential is limited by its poor solubility and bioavailability. Here, we develop inhalable chitosan-modified ASX-loaded PLGA nanoparticles (ASX@P@CS) to prevent RILI. This nanoformulation markedly improves the solubility of ASX, while the cationic chitosan modification enables mucin binding and tight-junction modulation, thereby enhancing the pulmonary permeability and retention. As a result, ASX@P@CS achieves superior intrapulmonary distribution, significantly attenuates acute oxidative damage and inflammation, and prevents chronic fibrotic remodeling in mouse models of RILI. This work establishes a biocompatible inhalable nano-astaxanthin platform with long-term biosafety, offering a promising strategy for the clinical prevention of radiation-induced lung injury.