三种递送体系对麝香草酚在致病菌胞内吸收的影响  

Effect of 3 delivery systems on the intracellular uptake of thymol in pathogenic bacteria

作　　者：徐谭芳 刘军锋 王平[3,5] 昝俊峰 杨可 田代志 陈茂华[4,5] XU Tan-fang;LIU Jun-feng;WANG Ping;ZAN Jun-feng;YANG Ke;TIAN Daizhi;CHEN Mao-hua(College of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065;Key Laboratory of Traditional Chinese Medicine Resources and Compounds,Ministry of Education,Hubei University of Chinese Medicine,Wuhan 430065;Engineering Research Center of the Ministry of Education on R&D of TCM Protection Technology and New Products for Elderly Brain Health,Hubei University of Chinese Medicine,Wuhan 430065;Yichang Hospital of Traditional Chinese Medicine,Yichang Hubei 443000;Hubei Shizhen Laboratory,Wuhan 430065)

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]湖北中医药大学中药资源与中药复方教育部重点实验室,武汉430065 [3]湖北中医药大学老年脑健康中医药防护技术与新产品研发教育部工程研究中心,武汉430065 [4]宜昌市中医医院,湖北宜昌443000 [5]湖北时珍实验室,武汉430065

出　　处：《中南药学》2024年第3期619-625,共7页Central South Pharmacy

基　　金：湖北中医药大学重大项目培育计划(No.2019ZXZ002);教育部高等学校博士学科点专项科研基金(No.20124230120004)。

摘　　要：目的研究阳离子-β-环糊精(C-β-CD)、羟丙基-β-环糊精(HP-β-CD)及10%乙醇三种药物递送体系对麝香草酚(THY)在大肠埃希菌和金黄色葡萄球菌内吸收的影响。方法采用倍半稀释法确定C-β-CD-THY、HP-β-CD-THY包合物和THY 10%乙醇溶液的最低抑菌浓度(MIC),通过生长曲线测定其抑菌活性,并采用高效液相色谱法建立THY的测定方法,测定大肠埃希菌和金黄色葡萄球菌对C-β-CD-THY、HP-β-CD-THY包合物和THY 10%乙醇溶液的胞内吸收量。运用扫描电镜分析两种细菌经药物处理后的形态学变化。结果THY 10%乙醇溶液、C-β-CD-THY和HP-β-CD-THY对大肠埃希菌的MIC分别为1.66、1.66、2.13 mmol·L^(-1),对金黄色葡萄球菌的MIC依次为0.83、0.83、1.66 mmol·L^(-1)。大肠埃希菌对C-β-CD-THY和HP-β-CD-THY的胞内吸收量分别为THY水溶液组的2.2倍和1.6倍,金黄色葡萄球菌对C-β-CD-THY和HP-β-CD-THY的胞内吸收量分别为THY水溶液组的6.5倍和5.5倍。经C-β-CDTHY和HP-β-CD-THY处理后,菌体表面皱缩凹陷,细胞膜破坏严重,大量细胞丧失完整性。结论环糊精包合物能破坏细菌细胞膜,增加THY在大肠埃希菌和金黄色葡萄球菌的胞内浓度,提高其生物利用度,环糊精及其衍生物可代替乙醇作为辅料,以发挥增溶、促透作用,并提高药物安全性。与HP-β-CD-THY相比,C-β-CD-THY包合物的抑菌效果更佳,可作为更高效的抑菌剂应用于食品药品等领域。Objective To determine the effect of cationic-β-cyclodextrin(C-β-CD),hydroxypropyl-β-cyclodextrin(HP-β-CD)and 10% ethanol delivery systems on the absorption of thymol(THY)in Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).Methods The minimum inhibitory concentration(MIC)of C-β-CD-THY,HP-β-CD-THY inclusion complexes and 10% ethanol solution of THY were determined with the doubled-and-half dilution method.The bacteriostatic activity was determined with growth curve.The intracellular uptake of C-β-CD-THY,HP-β-CD-THY inclusion complexes and THY 10% ethanol solution by E.coli and S.aureus were determined by HPLC.Scanning electron microscopy was used to analyze the morphological changes of the two bacteria after the drug treatment.Results The MICs of THY 10% ethanol solution,C-β-CD-THY and HP-β-CD-THY against E.coli were 1.66,1.66,and 2.13 mmol·L^(-1),respectively,and the MICs against S.aureus were 0.83,0.83,and 1.66 mmol·L^(-1).The intracellular uptake of C-β-CD-THY and HP-β-CD-THY by E.coli was 2.2 and 1.6 times higher than that of the THY water solution group.The intracellular uptake of C-β-CD-THY and HP-β-CD-THY by S.aureus was 6.5 and 5.5 times higher than that of the THY water solution group,respectively.Scanning electron microscopy revealed that C-β-CD-THY and HP-β-CD-THY treatment caused severe damage to the bacterial,resulting in crumpling and indentation and loss of cellular integrity.Conclusion Cyclodextrin inclusion complexes can disrupt bacterial cell membranes,increase the intracellular concentration of THY in E.coli and S.aureus,and enhance the bioavailability of THY.Cyclodextrins and their derivatives can be used as solubilizing excipients instead of ethanol to improve drug safety.The C-β-CD-THY inclusion complexes have better antimicrobial effect compared with HP-β-CD-THY,which can be used as an effective bacteriostatic agent in food and drugs.

关 键 词：阳离子-β-环糊精 羟丙基-Β-环糊精 麝香草酚 包合物 递送体系 

分 类 号：R283[医药卫生—中药学]