Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

由于呼吸道粘液通过捕获和清除异物颗粒而成为纳米载体的强大屏障，因此有效的粘膜递送仍然是一项主要挑战。纳米颗粒的表面性质决定了它们在呼吸道粘液中的保留和渗透能力。然而，尚未广泛研究纳米颗粒和粘液之间的相互作用以及这些相互作用如何影响分布。在这项研究中，负载黄ical素-磷脂复合物的聚合物纳米粒子被两种聚合物改性，即粘膜粘附性聚合物和粘液渗透性聚合物。对理化性质，粘液渗透，经上皮运输和组织分布进行了系统研究，以评估纳米颗粒与呼吸道的相互作用。两种纳米颗粒具有相似的粒径和良好的生物相容性，表现出持续释放的特性，但在zeta电位上显示出相当大的差异。有趣的是，穿透粘液的纳米颗粒在粘液中表现出更高的扩散速率，在粘液层中的渗透更深，增强了与粘膜粘附纳米颗粒相比，体外细胞摄取，药物在气道中的分布增加以及优异的局部分布和生物利用度。这些结果表明，粘液渗透性纳米颗粒在合理的输送系统设计中具有潜力，可通过促进粘液渗透并增加局部分布和生物利用度来提高吸入疗法的效率。