pH响应型Thanatin纳米抗菌药物的构建及其抑制产NDM-1酶耐药菌活性的研究  

Construction of pH-responsive Thanatin nano-antibacterial drug and its inhibitory activity on NDM-1 enzyme producing drug-resistant bacteria

作　　者：卢泽星 储著飞 王海波 邓晓军 LU Zexing;CHU Zhufei;WANG Haibo;DENG Xiaojun(Teaching and Research Section of Chemical Pharmacy,Department of Pharmacy,Air Force Medical University,Shaanxi,Xi’an 710032,China;Basic Chemistry Teaching and Research Section,Department of Pharmacy,Shaanxi University of Chinese Medicine,Shaanxi,Xi’an 712046,China)

机构地区：[1]空军军医大学药学系化学制药学教研室,陕西西安710032 [2]陕西中医药大学药学院基础化学教研室,陕西西安712046

出　　处：《中国医药科学》2024年第20期161-164,共4页China Medicine And Pharmacy

基　　金：国家自然科学基金(82104246)。

摘　　要：目的 设计一种纳米药物递送系统,以解决抗菌肽Thanatin因静脉注射生物利用度差而不能应用于治疗全身性感染疾病的限制。方法 以葡聚糖为基本骨架制备一种苯硼酸和原酸酯功能化的葡聚糖嵌段聚合物用于包载亲水性的Thanatin。结果 通过氮-硼配位作用实现Thanatin的有效封装,得到了一种粒径为190.8 nm、包封率和载药量分别为73.2%和11.6%的纳米药物;该纳米药物细胞毒性低,在pH为5.5、6.5的PBS中的半数释放时间分别为10 min和25 min,累积释放率超过90%。相对于游离的Thanatin,Thanatin纳米药物对产新德里金属-β-内酰胺酶-1(NDM-1)大肠杆菌感染所致败血症小鼠的治疗效果得到显著增强。结论对Thanatin进行纳米封装可增强循环稳定性,从而提高对败血症小鼠的治疗效果。Objective To design a nano-drug delivery system to solve the limitation that the antimicrobial peptide Thanatin cannot be used to treat systemic infectious diseases because of its poor bioavailability by intravenous injection.Methods A phenylboronic acid and orthoester functionalized chitosan block polymer was prepared using chitosan as the basic skeleton for encapsulating hydrophilic Thanatin.Results Thanatin was effectively encapsulated by nitrogen-boron coordination,and a nano-drug with a particle size of 190.8 nm,an encapsulation efficiency of 73.2%and a drug loading of 11.6%was obtained.The nano-drug had low cytotoxicity.The half-release time in PBS with pH of 5.5 and 6.5 was 10 min and 25 min respectively.Meanwhile,the cumulative release rate was over 90%.Compared with free Thanatin,the therapeutic efficacy of Thanatin nano-drug on septic mice caused by new delhi metallo-β-lactamase-1(NDM-1)-producing Escherichia coli infection was significantly enhanced.Conclusion Nano-encapsulation of Thanatin can enhance circulatory stability,thus improving the therapeutic efficacy on septic mice.

关 键 词：NDM-1酶 THANATIN 纳米药物 酸性pH响应 抗菌活性 

分 类 号：R91[医药卫生—药学]