黄连素温敏水凝胶的制备及其对牙周致病菌的抑菌作用评价  

Preparation of berberine-loaded thermo-sensitive hydrogels and evaluation of its antibacterial effect on periodontal bacteria

作　　者：柳玉梅 宋亚 吴娟[3] 梁惠强[4] 孙卫斌[3] LIU Yumei;SONG Ya;WU Juan;LIANG Huiqiang;SUN Weibin(Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China;China Pharmaceutical University, Nanjing 211198, China;Faculty of Dentistry,The University of HongKong,HongKong 999077,China.)

机构地区：[1]南京大学医学院附属口腔医院·南京市口腔医院中心实验室,江苏南京210008 [2]中国药科大学药学院,江苏南京211198 [3]南京大学医学院附属口腔医院·南京市口腔医院牙周科,江苏南京210008 [4]香港大学牙医学院,中国香港999077

出　　处：《口腔生物医学》2020年第2期97-101,共5页Oral Biomedicine

基　　金：国家自然科学基金(51772144);南京市卫生科技发展项目(YKK18121)。

摘　　要：目的:制备负载黄连素(BBR)的壳聚糖/β-甘油磷酸钠(CS/β-GP)温敏水凝胶,表征其基本理化性质,并对其生物学特性进行初步评价,评估其对慢性牙周炎的潜在治疗作用。方法:物理交联法制备CS/β-GP温敏水凝胶,包埋法制备25、50、100μg/mL BBR/CS/β-GP温敏水凝胶。以不含BBR的CS/β-GP温敏水凝胶为对照,表征成胶时间、pH、流变性能、微观形态和药物释放率。CCK8法检测各组水凝胶对牙周膜细胞增殖的影响。抑菌圈实验分析各组水凝胶对牙周致病菌牙龈卟啉单胞菌(P.gingivalis)、具核梭杆菌(F.nucleatum)的抑菌作用。结果:各组水凝胶在4℃均有良好的可注射性,人体体温时均可完成相变。CS/β-GP的相变温度37.26℃,各组水凝胶在37℃时3 min内可凝胶化,pH均在中性范围,扫描电镜观察为均一相互通联的网络结构。BBR/CS/β-GP水凝胶体外可以持续缓慢释放BBR,12 h累计释放率达70%~85%。各组凝胶与牙周膜细胞共培养1、3、5 d均显示良好的生物相容性;各组水凝胶对P.gingivalis和F.nucleatum均有抑菌作用,且抑菌作用随载药浓度增大而增强。结论:BBR/CS/β-GP具有良好的理化性质和生物学特性,且对牙周致病菌具有一定抑制作用,可以作为慢性牙周炎局部用药治疗的选择。Objective:To prepare berberine(BBR)-loaded chitosan/sodiumβ-glycerophosphate(CS/β-GP)thermosensitive hydrogels and investigate its basic physical,chemical properties and biological characteristics,to evaluate the potential role in the treatment of chronic periodontitis.Methods:CS/β-GP thermosensitive hydrogel was prepared by physical cross-linking,and BBR was added by embedding.According to the concentration of BBR,25,50,100μg/mL BBR/CS/β-GP thermosensitive hydrogel was prepared,and CS/β-GP thermosensitive hydrogel was used as a control to characterize each gel gelation time and pH,rheological properties,micromorphology and drug release rate.CCK8 method was used to detect the effects of hydrogels on the proliferation of periodontal ligament cells.The inhibition zone experiment was used to analyze each group's antibacterial effect of on periodontal pathogens Porphyromonas gingivalis(P.gingivalis)and Fusobacterium nucleatum(F.nucleatum).Results:Each group of gels had good injectability at 4℃,and phase transition completed around body temperature.The phase transition temperature of CS/β-GP was 37.26℃.The hydrogels of each group gelled within 3 minutes at 37℃.The pH is in the neutral range.The results of gel electron microscopy showed a uniform interconnected scaffold structure.BBR/CS/β-GP hydrogel can continuously release BBR slowly in vitro,and the cumulative release rate eached 70%-85%in 12 hours;co-cultivation of gels and periodontal ligament cells in each group showed good biological properties for 1,3 and 5 days;each group of hydrogels inhibited the growth of P.gingivalis and F.nucleatum.The greater the drug concentration,the stronger the antibacterial effect.Conclusions:BBR/CS/β-GP has better physical and chemical properties and biological characteristics,and has a certain bacteriostatic effect on periodontal pathogens.It can be used as a topical treatment option for chronic periodontitis.

关 键 词：黄连素 水凝胶 牙周炎 药物输送系统 

分 类 号：R781.4[医药卫生—口腔医学]