Study on the Airway Mucus Penetration Performance of Biodegradable Nanoparticles Based on Surface PEGylation in a Cystic Fibrosis Model

Cystic fibrosis (CF) airway mucus is thick and sticky, which makes it hard for nanoparticles to move and deliver drugs effectively. In this study, degradable PLGA nanoparticles were coated with polyethylene glycol (PEG) of different molecular weights (2, 5, and 10 kDa) to test their movement and depth of penetration in CF-like mucus. The nanoparticles had a uniform size of 150 ± 10 nm and were measured using fluorescence recovery after photobleaching (FRAP) and confocal imaging. The PEG (5 kDa) coating showed the best results, with a diffusion rate of 1.45 ± 0.12 µm²/s, about 3.8 times higher than that of uncoated particles. In a 6-hour test, the particles moved over 70% deeper into the mucus and showed much higher uptake by airway cells (P < 0.01). These results show that medium-length PEG chains reduce mucus adhesion and help nanoparticles move more easily through dense airway mucus. This work provides a practical way to improve drug carriers for CF and other lung diseases with mucus blockage.