PROJECT SUMMARY Mucus in our body naturally serves as a reservoir for antimicrobial peptides and antibodies. Inspired by this, the overall objective in this application is to develop synthetic mucus as a biomaterial platform for local delivery of biologics to mucosal tissues. Recently, we have engineered synthetic mucus (SM) biomaterials with properties comparable to natural mucus. The central hypothesis is these SM biomaterials can be used for local biologic drug delivery at mucosal sites. The central hypothesis will be tested by pursuing two specific aims: (1) Formulate therapeutic loaded SM and characterize their therapeutic effect in vitro and (2) Assess in vivo biodistribution and efficacy of SM mediated local therapeutic delivery. In the 1st aim, we will formulate SM with antimicrobial peptides and FDA-approved monoclonal antibodies. We will next confirm if these therapeutics can be loaded and retain their activity in vitro. In the 2nd aim, we will examine the distribution of biologic drugs in the colorectal and vaginal tract in mice following local SM mediated delivery. The efficacy of SM loaded with a TNF-targeting monoclonal antibody, clinically used in the treatment of inflammatory bowel diseases, will be evaluated in a mouse model of ulcerative colitis. The research proposed in this application is innovative as it offers a novel approach to deliver protein-based therapies to mucosal tissues. If successful, the results of this work will be significant as it may offer a safe and highly efficacious means to address infectious and inflammatory mucosal diseases.