硫酸头孢喹肟纳米凝胶的制备及对大肠杆菌的抗菌活性  

Preparation of cefquinome sulfate nanogels and antibacterial activity against Escherichia coli

作　　者：罗万和 鞠牧洁 冷楠楠 吾买尔江·牙合甫[1] 关鼎 周继萍 刘金环 韩俊成 LUO Wanhe;JU Mujie;LENG Nannan;WUMAIERJIANG·Yahefu;GUAN Ding;ZHOU Jiping;LIU Jinhuan;HAN Juncheng(Xinjiang Key Laboratory of New Drug Study and Creation for Herbivorous Animal,College of Veterinary Medicine,Xinjiang Agricultural University,Urumqi 830052,China;Laboratory of Animal Disease Diagnosis and Control Engineering,College of Animal Science and Technology,Tarim University,Alar,Xinjiang 843300,China)

机构地区：[1]新疆农业大学动物医学学院,新疆草食动物新药研究与创制重点实验室,新疆乌鲁木齐830052 [2]塔里木大学动物科学与技术学院,动物疫病诊断与防控工程实验室,新疆阿拉尔843300

出　　处：《中国兽医学报》2023年第6期1290-1296,共7页Chinese Journal of Veterinary Science

基　　金：新疆维吾尔自治区自然科学基金资助项目(2019D01B17);新疆农业大学校前期资助课题资助项目(XJAU201710);塔里木大学校长基金资助项目(TDZKSS202144);塔里木畜牧科技兵团重点实验室开放课题资助项目(HS202108)。

摘　　要：制备了一种可避免对胃肠道产生刺激并具有缓释作用的硫酸头孢喹肟纳米凝胶制剂,并评价其对大肠杆菌的抗菌活性。以2-羟丙基-β-环糊精、海藻酸钠和Ca^(2+)的浓度以及转速为变量,包封率(EE)和载药量(LC)为指标,筛选出最优配方,并对其外观性状、微观形态、Zeta电位、粒径和溶胀行为进行表征,同时采用微量肉汤稀释法测定其对大肠杆菌的最低抑菌浓度(MIC)并绘制杀菌曲线。结果显示,2-羟丙基-β-环糊精为30 g/L、海藻酸钠为30 g/L和Ca^(2+)为2 g/L,且转速为1200 r/min时,为最优配方;其EE和LC分别为(81.8±1.3)%和(54.3±0.8)%;其外观性状为澄清透明色,表现为凝胶状;扫描电镜结果显示硫酸头孢喹肟被包裹于所形成的网络结构中;平均粒径为(179.75±3.72)nm,Zeta电位为(-25.1±1.56)mV;所制备制剂在胃酸中具有较高的稳定性,在肠液中迅速发生溶胀;市售硫酸头孢喹肟注射液、硫酸头孢喹肟原料药和硫酸头孢喹肟纳米凝胶对大肠杆菌ATCC 25922的MIC分别为0.06,0.12,0.06 mg/L,对牛源大肠杆菌分离株的MIC分别为0.12,0.25,0.06 mg/L;体外杀菌曲线显示,硫酸头孢喹肟纳米凝胶对牛源大肠杆菌分离株表现出明显的质量浓度依赖性。结果表明,所制备的硫酸头孢喹肟纳米凝胶不仅可避免药物对胃肠道刺激反应,还通过缓释作用增强其对大肠杆菌的抗菌活性,进而为治疗由大肠杆菌引起的腹泻等疾病提供科学依据。To prepare a cefquinome sulfate nanogel which can avoid gastrointestinal irritation and has sustained-release effect,and evaluate its antibacterial activity against Escherichia coli(E.coli).With the concentration of 2-hydroxypropyl-β-cyclodextrin,sodium alginate,Ca^(2+)and rotational speedas variables,the optimal formula was selected with the entrapment efficiency(EE)and drug loading(LC)as indicators,and its appearance,micro morphology,zeta potential,particle size and swelling behavior were characterized.At the same time,the minimum inhibitory concentration(MIC)and in vitro the killing curves against E.coli were determined by broth microdilution method.The results showed that when 2-hydroxypropyl-β-cyclodextrin was 30 g/L,sodium alginate was 30 g/L and Ca^(2+)was 2 g/L,the prepared cefquinome sulfate nanogel was the optimal formula,and the EE and LC were(81.8±1.3)%and(54.3±0.8)%,respectively.Its appearance was clear and transparent,showing gel shape;scanning electron microscopy showed that cefquinome sulfate was encapsulated in the network structure;the average particle size was(179.75±3.72)nm and the Zeta potential was(-25.1±1.56)mV;It had high stability in gastric acid and rapid swelling in intestinal juice;the MIC of cefquinome sulfate injection,cefquinome sulfate and cefquinome sulfate nanogel against E.coli ATCC 25922 were 0.06,0.12 and 0.06 mg/L,against E.coli isolated from cattle were 0.06,0.12 and 0.06 mg/L,respectively;in vitro the killing curves showed that cefquinome sulfate nanogel against E.coli isolate was obvious concentration-dependence.Therefore,the cefquinome sulfate nanogel prepared in this study can not only avoid the drug's response to gastrointestinal irritation,but also enhance its antibacterial activity against E.coli through sustained-release,thus providing reference materials for the treatment of diarrhea caused by E.coli.

关 键 词：大肠杆菌 硫酸头孢喹肟 纳米凝胶 抗菌活性 制备 

分 类 号：S852.61[农业科学—基础兽医学] S859[农业科学—兽医学]