Caffeic Acid and\nCyclen-Based Hydrogel for Synergistic\nAntibacterial Therapy

Caffeic acid is a natural product that contains both\nphenolic and\nacrylic functional groups and has been widely employed as an alternative\ndrug to combat chronic infections induced by microbes such as bacteria,\nfungi, and viruses. Several strategies, including derivatization and\nnanoformulation, have been applied in order to overcome the issues\nof water insolubility, poor stability, and the bioavailability of\ncaffeic acid. Here, caffeic acid and cyclen-Zn(II) are incorporated\ninto a G<sub>4</sub>-assembly by using a phenylborate linker to form\nthe mixed supramolecular prodrug <b>GB-CA/Cy-Zn(II)</b> hydrogel.\nThe delivery system is expected to enhance antibacterial and anti-inflammatory\nproperties during the wound healing process through the synergistic\neffect of caffeic acid and cyclen-Zn(II). The preparation and physicochemical\nand mechanical properties of the hydrogel were investigated by NMR,\nCD, TEM, and rheological assays. The typical inflammatory cytokines\nand <i>in vitro</i> antibacterial experiments indicated\nthat inflammation and infection can be significant suppressed by the\nhydrogel treatment. An <i>in vivo</i> infected wound model\ntreated by the hydrogel showed rapid wound healing capacity and biosafety.\nThe current work depicts a simple method to prepare a caffeic acid\nhydrogel carrier, which facilitates synergistic treatment for inflammation\nand bacterial infections at the wound site.