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Mucoadhesion is a special case of bioadhesion in which a material adheres to soft mucosal tissues. This review elucidates our current understanding of mucoadhesion across length, time, and energy scales by focusing on relevant structural features of mucus. We highlight the importance of both covalent and non-covalent interactions that can be tailored to maximize mucoadhesive interactions, particularly concerning proteinaceous mucoadhesives, which have been explored only to a limited extent so far in the literature. In particular, we highlight the importance of thiol groups, hydrophobic moieties, and charged species inherent to proteins as key levers to fine tune mucoadhesive performance. Some aspects of protein surface modification by grafting specific functional groups or coupling with polysaccharides to influence mucoadhesive performance are examined. Insights from this review offer a physicochemical roadmap to inform the development of biocompatible, protein-based mucoadhesive systems that can fulfil dual roles for both adhesion and delivery of actives, enabling the fabrication of advanced biomedical, nutritional and allied soft material technologies. • Mucoadhesive interactions occurs across length and strength scales. • The structure of mucins and mucus gel properties may dictate mucoadhesion. • Proteins' isoelectric point and surface hydrophobicity influence mucoadhesive force. • Thiol groups are inherent to some proteins and are related to enhanced mucoadhesion. • Combining proteins and polysaccharides lead to mucoadhesives with new features.
Hazt et al. (Mon,) studied this question.