Fe2O3 nanoparticles disrupt microstructure and reduce viscoelasticity of simulated asthma airway mucus towards potential airway mucus clearance applications

Jiayuan Zhong¹Lei Shi²Zhiwei Liu³Kai Ni¹Lei Liu¹Yan Pan¹Jingjing Li¹Xiaowei Yu²Linhong Deng^1*Mingzhi Luo^1*

• ¹Changzhou University, Changzhou, Jiangsu Province, China
• ²Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No 2 People's Hospital of Nanjing Medical University, Changzhou, China
• ³Wenzhou Key Laboratory of Biomaterials and Engineering, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China

Fe2O3 nanoparticles have been developed as drug carriers that can be transported through airway mucus, but their own impact on rheological properties of airway mucus especially in disease states is unknown. We investigated the capacity of Fe2O3 nanoparticles dispersed in various media to alter the microstructure and rheological behaviors of simulated asthmatic airway mucus (AM). AM was prepared with reconstituted mucins and other components in a composition resembling human airway mucus in asthma as reported, and then treated with Fe2O3 nanoparticles before and after curing.Subsequently, AM treated with or without Fe2O3 nanoparticles was examined for microstructure by optical immunofluorescence microscopy, and rheological behaviors by steady state and dynamic rotational rheometry. The results showed that Fe2O3 nanoparticles disrupted the mucus microstructure by inducing protein aggregation and thus increasing pore size and fiber diameter of the AM. On the other hand, Fe2O3 nanoparticles significantly reduced the magnitude of viscoelastic properties including apparent viscosity, yield stress, and dynamic viscoelastic modulus of AM. Although Fe2O3 nanoparticles added to the curing or the cured AM appeared to cause similar effects, the effects were usually greater in magnitude if the nanoparticles were added to the curing AM.The effects were also dependent on concentration and surface property determined by the dispersion medium of the nanoparticles, which indicates that Fe2O3 nanoparticles dispersed at 0.4 mg/mL in H2O were most potent in altering microstructure and rheology of AM, and were even better than 0.4 mg/mL conventional mucolytics chymotrypsin. Further tests with mucus samples collected from asthmatic patients showed similar results as with AM. Taken together, these findings suggest that Fe2O3 nanoparticles per se can not only be used as drug carriers, but also as expectorant agents for airway mucus clearance therapy, which may be advantageous to pharmaceutical mucolytics due to their wide availability and high biocompatibility.