Solid phase synthesis of oxidized sodium alginate-tobramycin conjugate and its application for infected wound healing

Although sodium alginate possesses excellent biocompatibility, moisture retention and easy availability, it cannot be directly applied for infected wound treatment. Herein, a solid phase synthesis strategy was proposed to fabricate oxidized sodium alginate-tobramycin conjugate (OSA-TOB) for anti-infection dressing development. 13C nuclear magnetic resonance spectra indicated that the oxidization process does not change the ratio of β-D-mannuronic acid (M) / α-L-guluronic acid (G) in OSA and the oxidization reaction shows no stereoselectivity. Elemental analysis disclosed that the graft ratio of tobramycin in OSA-TOB is 13.8 %. Antibacterial test indicated that OSA-TOB can effectively inhibit four prevalent pathogenic bacterial S.epidermidis, P. aeruginosa, S. aureus and E. coli via a different antibacterial mechanism compared to the original TOB. Hemolysis and cytotoxicity assays shown that OSA-TOB have superior hemocompatibility and cytocompatibility. Infected wound healing assay shown that the healing rate of OSA-TOB is the highest. Further analysis indicated that OSA-TOB can reduce the local inflammatory response, accelerate the form of epithelium and collagen deposition. In conclusions, OSA-TOB synthesized in solid phase can be potentially applied as a promising anti-infection wound dressing.