Engineering of targeting antioxidant polypeptide nanopolyplexes for the treatment of acute lung injury

The pathogenesis of acute lung injury (ALI) involves various mechanisms, such as oxidative stress, inflammation, and epithelial cell apoptosis. However, current drug therapies face limitations due to issues like systemic distribution, drug degradation in vivo, and hydrophobicity. To address these challenges, we developed a pH-responsive nano-drug delivery system for delivering antioxidant peptides to treat ALI. In this study, we utilized low molecular weight chitosan (LMWC) and hyaluronic acid (HA) as carrier materials. LMWC carries a positive charge, while HA carries a negative charge. By stirring the two together, the electrostatic adsorption between LMWC and HA yielded aggregated drug carriers. To specifically target the antioxidant drug WNWAD to lung lesions and enhance therapeutic outcomes for ALI, we created a targeted drug delivery system known as HA/LMWC@WNWAD (NPs) through a 12-h stirring process. In our research, we characterized the particle size and drug release of NPs. Additionally, we assessed the targeting ability of NPs. Lastly, we evaluated the improvement of lung injury at the cellular and animal levels to investigate the therapeutic mechanism of this drug targeting delivery system.