Using mucus for localized drug delivery in inflammatory bowel disease treatment

Inflammatory bowel disease (IBD) causes recurrent inflammation in the gastrointestinal tract. While tumor necrosis factor (TNF)-neutralizing monoclonal antibodies (mAbs) have emerged as an effective biologic that mitigates IBD remission, limitations in mAb delivery — where only a fraction of the administered dose reaches its target — raise therapeutic costs. In addition, the broad immunosuppressive effects of systematic mAb delivery increases the risk of secondary infections.

To address these challenges, Yeruva et al. explored the use of mucus for localized mAb delivery.

“Mucus is a highly underappreciated component of human physiology,” said author Gregg Duncan. “We were motivated by its innate function to promote health by clearing pathogens and serving as a reservoir of bioactive species such as antimicrobial peptides and antibodies.”

The authors developed synthetic mucus (SM) gels loaded with mAbs and found that under conditions similar to the gastrointestinal tract, degradation of the mucin network breaks down the gel structure and allows for controlled drug release. They also discovered how SM gel alone dampens the pro-inflammatory phenotype of macrophages without suppressing anti-inflammatory function, indicating an immunomodulatory role.

By modulating gel physical properties and examining their impact on therapeutic efficacy, the authors found that the stiffness and crosslinking density of the SM gel regulate drug release kinetics and macrophage behavior, in turn influencing the cost-effectiveness and safety of mAb therapies in IBD.

Next, the authors plan to explore the immunomodulation potential of mucin, which has induced globalized dampening of macrophage activity in controls.

“Future work will focus on testing the hypothesis that interactions between mucin-associated glycans and Siglec receptors drive anti-inflammatory signaling in macrophages,” said author Taj Yeruva. “More broadly, we anticipate growing interest in leveraging glycan-receptor interactions to engineer mucus-inspired materials with tunable immune functions.”

Source: “Synthetic mucus biomaterials enable localized therapeutic antibody delivery in inflammatory bowel disease,” by Taj Yeruva, Sydney Yang, Michele Kaluzienski, Rebecca Louisthelmy, Shadin Doski, Katharina Maisel, and Gregg A. Duncan, APL Bioengineering (2026). The article can be accessed at https://doi.org/10.1063/5.0297897 .