{"doi":"10.1101/2025.08.15.670558","title":"Synthetic Mucus Biomaterials Enable Localized Therapeutic Antibody Delivery in Inflammatory Bowel Disease","abstract":"Abstract Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent gastrointestinal inflammation that requires long-term therapeutic intervention. While anti-TNF-α 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-α-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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":572965,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1039328,"name":"Sydney Yang","orcid":"0000-0001-5561-3152","position":1,"is_corresponding":false},{"id":1122944,"name":"Michele L. Kaluzienski","orcid":null,"position":2,"is_corresponding":false},{"id":1479842,"name":"Rebecca Louisthelmy","orcid":null,"position":3,"is_corresponding":false},{"id":1039781,"name":"Shadin Doski","orcid":null,"position":4,"is_corresponding":false},{"id":714564,"name":"Katharina Maisel","orcid":"0000-0002-3560-9751","position":5,"is_corresponding":false},{"id":332709,"name":"Gregg A. Duncan","orcid":"0000-0002-6811-1327","position":6,"is_corresponding":false},{"id":1039327,"name":"Taj Yeruva","orcid":"0000-0001-9717-0812","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40894802","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}