Glucose-sensitive delivery of tannic acid by a photo-crosslinked chitosan hydrogel film for antibacterial and anti-inflammatory therapy
Junyu Liu, Haifeng Liu, Yongliang Jia, Ziwei Tan, Ruixia Hou, Jie Lu, Dongmei Luo, Xinyu Fu, Lu Wang, Xiangyu Wang
Abstract
A glucose-sensitive antibacterial and anti-inflammatory hydrogel film with controlled release of tannic acid (TA) was synthesized using chitosan (CS). Specifically, the photo-crosslinked CS hydrogel was first obtained and then immersed in TA solution to generate composite hydrogel film with enhanced mechanical properties. Subsequently, N-hydroxysuccinimide/1-ethyl-3-(3-dimethylaminopropyl) carbodiimide based coupling chemistry was used to covalently crosslink glucose oxidase (GOx) to CS to obtain glucose sensitivity. The physicochemical properties, including chemical composition, enzyme-related characteristics, glucose responsiveness, and mechanical strength, were thoroughly investigated, followed by the cytotoxicity, antibacterial and anti-inflammatory tests. The results showed that the GOx immobilized on the film surface by covalent bonding gave better stability than those that were physically adsorbed. In addition, it could quickly and correspondingly modify its inner pore structure in response to the glucose stimulus and then control the loaded TA release. Meanwhile, the TA addition could enhance the film's mechanical properties. The composite hydrogel film demonstrated adequate biocompatibility and can inhibit NO, IL-6, and TNF-α production in stimulated macrophages, as well as Porphyromonas gingivalis growth, demonstrating effective antibacterial and anti-inflammatory activity.