Caffeic Acid and Cyclen-Based Hydrogel for Synergistic Antibacterial Therapy

Caffeic acid is a natural product that contains both phenolic and acrylic functional groups and has been widely employed as an alternative drug to combat chronic infections induced by microbes such as bacteria, fungi, and viruses. Several strategies, including derivatization and nanoformulation, have been applied in order to overcome the issues of water insolubility, poor stability, and the bioavailability of caffeic acid. Here, caffeic acid and cyclen-Zn(II) are incorporated into a G₄-assembly by using a phenylborate linker to form the mixed supramolecular prodrug <b>GB-CA/Cy-Zn(II)</b> hydrogel. The delivery system is expected to enhance antibacterial and anti-inflammatory properties during the wound healing process through the synergistic effect of caffeic acid and cyclen-Zn(II). The preparation and physicochemical and mechanical properties of the hydrogel were investigated by NMR, CD, TEM, and rheological assays. The typical inflammatory cytokines and <i>in vitro</i> antibacterial experiments indicated that inflammation and infection can be significant suppressed by the hydrogel treatment. An <i>in vivo</i> infected wound model treated by the hydrogel showed rapid wound healing capacity and biosafety. The current work depicts a simple method to prepare a caffeic acid hydrogel carrier, which facilitates synergistic treatment for inflammation and bacterial infections at the wound site.