Multi-Parameter Analysis of Nanoparticle Size Optimization and Mucus Penetration Efficiency Using a Microfluidic Platform

This study used a PDMS microfluidic chip to study how nanoparticle size and surface wettability affect their movement in airway mucus. Artificial mucus with 3% mucin was used to test nanoparticles ranging from 50 nm to 300 nm in size and with contact angles between 40° and 90°. When the particle size was smaller than 150 nm and the contact angle was below 60°, the diffusion coefficient increased about 2.7 times, and the retention time in mucus dropped by nearly 45%. A simple regression model combining particle size and contact angle showed strong agreement with experimental data ( ), allowing clear prediction of transport efficiency. Unlike earlier static or single-factor tests, this microfluidic system provided a stable and repeatable environment close to airway conditions. The results offer practical guidance for designing nanoparticles that can cross mucus barriers and improve inhaled drug delivery. Future work should test real human mucus and include ciliary movement to verify the model under physiological conditions.