Fluorinated hyaluronates endow oral nanoparticles with mucus penetration and colonic macrophage targeting properties

The therapeutic outcomes of oral nanotherapeutics against ulcerative colitis (UC) are compromised by their shortage of mucus-penetrating and macrophage-targeting properties. Herein, hyaluronate (HA) was fluorinated and used to functionalize the surface of curcumin (CUR)-loaded polymeric nanoparticles (NPs). The generated FHA-CUR-NPs had hydrodynamic diameters of 172.9 ​nm and negatively charged surfaces (-17.5 ​mV). It was found that the fluorination of NPs could improve their mucus-penetrating capacity and yield an obviously higher cell internalization percentages in macrophages than their counterparts (CUR-NPs and HA-CUR-NPs), resulting in the strongest capacity to decrease the secreted amounts of the typical pro-inflammatory cytokines (TNF-α, IL-6, and IL-12). In vivo investigations suggested that oral administration of hydrogel (chitosan/alginate)-encapsulating FHA-CUR-NPs preferentially accumulated in the colitis tissues and achieved much better therapeutic outcomes against UC, in comparison with hydrogel-embedding CUR-NPs or HA-CUR-NPs. Collectively, FHA-CUR-NP-based system with mucus-penetrating and macrophage-targeting capacities is a potential oral platform for UC treatment.