Combined Antioxidant-Antibiotic Treatment for Effectively Healing Infected Diabetic Wounds Based on Polymer Vesicles.

Abstract

Infected diabetic wounds are difficult to heal due to high reactive oxygen species (ROS) concentrations and recurrent infections. Such wounds can easily deteriorate into a diabetic ulcer, a chronic diabetic complication with a very high mortality rate. Herein, we propose a combined antioxidant-antibiotic therapy based on poly(ε-caprolactone)-<i>block</i>-poly(glutamic acid) polymer vesicle to treat infected diabetic wounds. This was realized by <i>in situ</i> decoration of stable, well-dispersed ceria nanoparticles onto ciprofloxacin (CIP)-loaded polymer vesicles. These resulting CIP-loaded and ceria-decorated polymer vesicles (CIP-Ceria-PVs) exhibited high superoxide dismutase mimetic activity to inhibit superoxide free radicals (the inhibition rate reached ∼50% at an extremely low cerium concentration of 1.25 μg/mL). When the cerium content is in the range of 5-20 μg/mL, the CIP-Ceria-PVs showed the highest protective capability to normal L02 cells from damage of superoxide free radicals. In addition, the CIP-Ceria-PVs exhibited enhanced antibacterial activity (the dosage of CIP in CIP-Ceria-PVs was reduced by 25-50% compared to free CIP). <i>In vivo</i> treatment of infected diabetic wounds was performed on a diabetic mice model. The CIP-Ceria-PVs could effectively cure infected diabetic wounds within 14 days. Overall, a combined antioxidant-antibiotic therapy was proposed by introducing ceria nanoparticles and CIP into polymer vesicles for the treatment of infected diabetic wounds.