Mucoadhesion across scales: Towards the design of protein-based adhesives

Abstract

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.

Highlights

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.

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Table 3. Protein or peptide-polysaccharide-based systems interacting with mucus/mucin.

Protein/ peptide type	Polysaccharide type	Mucin type	Conditions/modification used	Nature of interaction (adhesive with mucin/mucus)
Homocysteine	Poly(acrylic acid)	Native porcine intestinal mucosa	Protein/polymer conjugate in the form of tablets	Covalent (disulfide bond)
Gelatin	λ-carrageenan	Mucin from porcine stomach	Protein/polymer mixture in the form of films and microspheres	Not specified
WPI	Alginate	Native rabbit intestinal mucosa	Protein/polymer microparticles	Electrostatic (negatively charged adhesive)
Gelatin, Keratin	Chitosan	Native sheep buccal mucosa	Proteins/polymer composite films	Electrostatic (positively charged adhesive) Covalent (disulfide bond)
Lysozyme	Starch	Native rat intestinal and stomach mucosa	Lysozyme nanoparticles incorporated into oxidized starch microgels	Electrostatic (negatively charged adhesive)
BSA	Chitosan	Native cow buccal mucosa	Thiolated BSA combined with chitosan into buccal patches	Electrostatic (positively charged adhesive) Covalent (disulfide bond)
Mucin	Mucin glycan *	Mucin from bovine submaxillary	Mucosome nanoparticles	Not specified

* Inherent glycosylation of mucin

Bianca Hazt, Daniel J. Read, Oliver G. Harlen, Wilson C.K. Poon, Adam O’Connell, Anwesha Sarkar, Mucoadhesion across scales: Towards the design of protein-based adhesives, Advances in Colloid and Interface Science, Volume 334, 2024, 103322, ISSN 0001-8686, https://doi.org/10.1016/j.cis.2024.103322.