Nanoparticle-Mediated Strategies for Enhanced Drug Penetration and Retention in the Airway Mucosa

Airway mucus is a complex viscoelastic gel composed mainly of water, glycoproteins, lipids, enzymes, minerals, etc. Among them, glycoproteins are the main factors determining mucus's gel-like rheology. Airway mucus forms a protective barrier by secreting mucin, which represents a barrier for absorption, especially for more lipophilic drugs. It rapidly removes drugs from the airway through the physiological mucus clearance mechanism so drugs cannot remain in the lungs or reach the airway epithelial tissue for a long time. Significant progress has been made in enhancing drug lung deposition recently, but strategies are still needed to help drugs break through the lung mucosal barrier. Based on the physiopathological mechanisms of airway mucus, this paper reviews and summarizes strategies to enhance drug penetration and retention in the airway mucosa mediated by nano-delivery systems, including mucosal permeation systems, mucosal adhesion systems, and enzyme-modified delivery systems. On this basis, the potential and challenges of nano-delivery systems for improving airway mucus clearance are revealed. New ideas and approaches are provided for designing novel nano-delivery systems that effectively improve drug retention and penetration in the airway mucus layer.