Overcoming the mucus barrier: Optimization design of carriers to enhance mucus permeability, targeting, and responsiveness.

The mucus layer is distributed in various tissues of the human body. It serves as a key barrier that hinders the permeation of carriers and the adsorption of their loaded bioactive components (BCs). However, the impact factors of nanoparticles' mucus penetration and how they guide the optimization design of carrier are not clear. In this review, we revealed the factors affecting the mucus permeability of nanoparticles (NPs) and summarized the optimization design of organ-targeted or responsive NPs. The NPs' mucus penetration was related to the properties of NPs, including size, surface charge, hydrophilicity, shape, stiffness, and grafted density of modified groups, and the environments of the mucus layer, including pH and ion concentration. Specifically, the high pH in mucus, small size, zwitterionic and hydrophilic surface properties, rod shape, and semi-elastic stiffness of NPs are favorable conditions for their mucus penetration to achieve effective BCs delivery. Furthermore, some targeting and responsive carrier designs have emerged in the application of mucosal systems, such as the gastrointestinal tract, buccal tissue, airway, nose, and eye. Modification of carbohydrates, peptides, and bacteria membrane, and engineered bacteria help to target tumor cells, bacteria, and inflammatory factors for cancer therapy, inflammatory treatment, and bacteria-infection recovery, respectively. The conclusion and discussion of impact factors of NPs' mucus penetration and examples of the targeting and responsive design of carriers would help to inspire the optimization design of carriers applied in bioactive components delivery.