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bioRxiv · 10.1101/2025.08.15.670558

Synthetic Mucus Biomaterials Enable Localized Therapeutic Antibody Delivery in Inflammatory Bowel Disease

Yeruva, T.·Yang, S.·Kaluzienski, M.·Louisthelmy, R.·Doski, S.·Maisel, K.·Duncan, G.
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Abstract

Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent gastrointestinal inflammation that requires long-term therapeutic intervention. While anti-TNF- monoclonal antibodies (mAbs) are effective in maintaining remission in IBD, systemic delivery is associated with immunosuppression, poor targeting efficiency, and high cost. To address these limitations, we developed a synthetic mucin-based hydrogel for localized delivery of TNF--targeting mAbs. Mucins are heavily glycosylated biopolymers that naturally bind antimicrobial and anti-inflammatory proteins, making them well-suited for local biologic drug delivery at mucosal sites. Synthetic mucin-based hydrogels were formed by crosslinking mucin harvested from porcine small intestine with a 4-arm PEG-thiol and loaded with mAbs to evaluate biocompatibility, antibody release kinetics, and therapeutic efficacy. In vitro studies confirmed cytocompatibility of mucin-based hydrogels and demonstrated sustained release of full-length IgG antibodies, with enhanced release under proteolytic conditions simulating the gastrointestinal environment. Moreover, mucin-based hydrogels alone were found to modulate macrophage activation and dampen inflammation in LPS-stimulated macrophages. Treatment of LPS-stimulated macrophages with mAb-loaded hydrogels reduced pro-inflammatory cytokine production and macrophage activation, confirming retention of mAb bioactivity. Compared to antibodies administered in solution, in vivo biodistribution studies revealed greater absorption of antibodies when loaded in mucin-based hydrogels and administered via enema in TNBS-induced colitis mice likely due to enhanced adhesion to mucosal epithelium and slowed intestinal clearance. This study demonstrates the potential of mucin-based hydrogels as a platform for local mAb delivery in IBD, enabling targeted immunosuppression while minimizing systemic exposure.

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Yeruva, T., Yang, S., Kaluzienski, M., Louisthelmy, R., Doski, S., Maisel, K., Duncan, G.. 2025-08-21. Synthetic Mucus Biomaterials Enable Localized Therapeutic Antibody Delivery in Inflammatory Bowel Disease. https://doi.org/10.1101/2025.08.15.670558

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