Synthetic Mucus Hydrogels for Antimicrobial Peptide Delivery and Treatment of Bacterial Infections

Abstract

Antibiotic resistant infections have the propensity to form biofilms that contribute to chronic infections and result in hyper-inflammatory response in tissues. Recent studies pose antimicrobial peptides (AMPs) as alternatives to antibiotics and to modulate inflammatory response. However, AMPs have a short half-life due to rapid clearance and degradation reducing AMP bioavailability and efficacy. In the human body, AMPs interact and may associate with mucins which result in the sequestering of AMPs within mucus. Previously, we have developed a synthetic mucus (SM) hydrogel inspired by the innate properties of mucins. The objective of this work was to evaluate the SM hydrogel as a tool for local antimicrobial peptide delivery of LL37 to enhance the treatment for infection and inflammation. To study this, we (1) assessed the release of LL37 and antimicrobial activity of LL37 loaded SM (LL37-SM) hydrogels on Pseudomonas aeruginosa, (2) evaluated the antibiofilm activity of LL37-SM hydrogel treatment on Pseudomonas aeruginosa biofilms, and (3) determined the impact of LL37-SM hydrogel treatment on RAW 264.7 macrophage activation and phagocytic activity. The association of LL37 to SM hydrogels enabled the sustained release of LL37 over 8 hours and retained antimicrobial activity. Treatment with LL37-SM hydrogels for 24 hours disrupted biofilm growth and resulted in a mixed inflammatory response in macrophages. Our results highlight the antimicrobial, antibiofilm, and potentially inflammatory modulating capabilities of SM hydrogels which can further inform the use of mucins in bioactive biomaterials for biomedical applications.