Mucus is a hydrogel that exhibits complex selective permeability, permitting the passage of some particles while restricting the passage of other particles including important therapeutics. In this review, we discuss biochemical mechanisms underlying mucus penetration and mucus binding, emphasizing the importance of steric, electrostatic, and hydrophobic interactions. We discuss emerging techniques for engineering nanoparticle surface chemistries for mucus penetration as well as recent advances in tuning mucus interactions with small molecule, peptide, or protein therapeutics. Finally, we highlight recent work suggesting that mucus permeability can serve as a biomarker for disease and physiological states such as pregnancy.
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