Bacteria-mimetic Bap1-chitosan bioadhesive achieves >400 J m-2 mucoadhesion for enhanced drug delivery.

Effective drug delivery to mucus-lined tissues, such as those affected by mucosal inflammatory diseases, remains a significant challenge. Current mucoadhesive strategies often rely on covalent bonding, which can lead to instability, cytotoxicity, and incompatibility with sensitive therapeutics. This limits their utility in applications like tissue repair and targeted drug delivery to inflamed regions. A need exists for bioadhesives that offer strong, durable adhesion while maintaining biocompatibility and enabling efficient drug transport, ideally through mechanisms that avoid tissue damage.

Researchers developed a bacteria-mimetic bioadhesion strategy by grafting a short Bap1-derived adhesion peptide onto chitosan. This engineered material was designed to leverage multivalent, cooperative secondary bonding for enhanced mucus interactions, mimicking the adhesion mechanisms of Vibrio cholerae. The team assessed the bioadhesive's performance by measuring adhesion energy on porcine intestine and evaluating its compatibility with a tough hydrogel matrix. They also performed confocal imaging to quantify tissue penetration and ex vivo intestinal delivery and in vitro drug release tests to compare drug transport and tissue exposure against a conventional carbodiimide-mediated covalent bonding strategy. Cytocompatibility was also evaluated.

The novel Bap1-chitosan bioadhesive demonstrated significantly increased adhesion energy on porcine intestine. When integrated with a tough hydrogel matrix, it achieved adhesion energies exceeding 400 J m-2 without forming covalent bonds to the tissue, indicating robust yet non-damaging attachment. Confocal imaging revealed deep tissue penetration of approximately 80 µm, coupled with markedly enhanced mucin binding, suggesting effective interaction with the mucosal layer. Crucially, the bioadhesive exhibited no loss of cytocompatibility, confirming its safety profile. >Compared to carbodiimide-mediated covalent bonding, the Bap1-chitosan strategy led to improved drug transport and tissue exposure in ex vivo intestinal delivery and in vitro drug release tests, highlighting its potential for superior therapeutic efficacy.