Enzyme‐Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes

Abstract Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme‐responsive nanoparticles for the targeted delivery of an anti‐inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently‐labeled, dexamethasone‐loaded peptide‐polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub‐periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles‐treated rats, compared to control groups injected with free dexamethasone and non‐responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme‐responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.