State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, Section 3, Ren Min Nan Rd., Chengdu 610041, Sichuan, China; Shanxi Medical University School and Hospital of Stomatology, No.63, Xin Jian Nan Rd., Taiyuan 030001, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, Section 3, Ren Min Nan Rd., Chengdu 610041, Sichuan, China.
Int J Biol Macromol. 2019 Feb 1;122:19-28. doi: 10.1016/j.ijbiomac.2018.09.202. Epub 2018 Oct 1.
A novel glucose-sensitive drug delivery system with controlled release of metronidazole was synthesized by using biocompatible photo-crosslinked chitosan hydrogel film. Specifically, methacrylic anhydride, as photosensitive substance, was firstly grafted on chitosan molecular chains and then UV irradiation was applied as the crosslinking method. Glucose sensitivity was endowed by immobilizing glucose oxidase on the surface of chitosan film. The physicochemical characteristics including chemical composition, crosslinking degree, mechanical strength and related enzyme properties were investigated successively. Cytotoxicity test, drug release and anti-bacterial test were carried out, respectively. The results show that this photo-crosslinked hydrogel film has good mechanical properties; meanwhile, the immobilized enzyme's bonding capacity and activity can maintain a relatively high level after surface activation. In addition, this material possesses better biocompatibility than chemical crosslinked samples. What's more, it can sense the ambient glucose stimulus, rapidly and correspondingly adjust its inner pore structure to control the loaded metronidazole release, lead to an improved antimicrobial activity against Porphyromonas gingivalis under high glucose concentration. This glucose sensitive hydrogel film may provide a promising method for diabetic's periodontitis therapy in clinic.
一种新型的葡萄糖敏感药物输送系统,通过使用生物相容性的光交联壳聚糖水凝胶膜来控制甲硝唑的释放。具体而言,首先将光敏物质甲基丙烯酐接枝到壳聚糖分子链上,然后应用紫外光照射作为交联方法。通过在壳聚糖膜表面固定葡萄糖氧化酶赋予葡萄糖敏感性。随后对包括化学组成、交联度、机械强度和相关酶性质在内的物理化学特性进行了研究。分别进行了细胞毒性试验、药物释放和抗菌试验。结果表明,这种光交联水凝胶膜具有良好的机械性能;同时,固定化酶的结合能力和活性在表面活化后仍能保持较高水平。此外,与化学交联样品相比,该材料具有更好的生物相容性。更重要的是,它可以感知环境中的葡萄糖刺激,迅速相应地调整其内部孔结构,以控制负载的甲硝唑释放,从而在高葡萄糖浓度下提高对牙龈卟啉单胞菌的抗菌活性。这种葡萄糖敏感水凝胶膜可能为临床治疗糖尿病性牙周炎提供一种有前途的方法。