Multifunctional antibiotic hydrogel doped with antioxidative lycopene-based liposome for accelerative diabetic wound healing

In the daily management of infected diabetic wound, antibiotics resistance derived from broad-spectrum antimicrobe is still inevitable. Together with the complicated inflammatory environment induced by hyperglycemia and bacteria colonization, it's urgent to develop a novel bioactive ingredient integrating both anti-oxidative and modulation on inflammatory environment to be combined with disinfection. In regard of this, lycopene (LYC), an abundant, natural and unsaturated alkene carotenoid extracted from tomatoes was intercalated into the Dipalmitoyl-phosphatidylcholine (DPPC) liposomes loading with tobramycin (TOB), and further formulated with HAMA hydrogel (LT NPs@Gel) to prepare a novel multifunctional antibiotic wound dressing. The in vitro study showed that the intercalation of LYC and the loaded TOB brought LT NPs antioxidative and antibacterial properties, thus effectively inhibit the proliferation of bacteria and relieve endoplasmic reticulum (ER) stress to promote cell migration and angiogenesis. In an infected diabetic wound model on rat, the local administration of LT NPs@Gel significantly promoted wound healing within 14 days. Owing to the synchronized management on the inflammation environment and bacteria colonization, the massive oxidative stress in the wound were significantly alleviated, followed by the distinctive promotion of angiogenesis, re-epithelization, and collagen deposition. We believe that this functional hybrid HAMA hydrogel formulated with novel LYC-intercalated antibiotic liposome can achieve the multi-dimensional management of infected diabetic wounds.