负载环丙沙星及利福平的聚合物胶束制备及其抗菌性能分析  

Preparation and antibacterial activity analysis of ciprofloxacin and rifampicin-loaded polymer micelles

作　　者：何清玲 陈柳婷 孙泽月 刘飞[2] 卢嘉驹 孔祥东[1] HE Qingling;CHEN Liuting;SUN Zeyue;LIU Fei;LU Jiaju;KONG Xiangdong(School of Materials Science&Engineering,Zhejiang Sci-Tech University,Hangzhou 310018,China;Zhejiang Hospital of lntegrated Traditional Chinese and Western Medicine,Hangzhou 310003,China)

机构地区：[1]浙江理工大学材料科学与工程学院,杭州310018 [2]浙江省中西医结合医院骨科,杭州310003

出　　处：《浙江理工大学学报（自然科学版）》2024年第5期579-587,共9页Journal of Zhejiang Sci-Tech University(Natural Sciences)

基　　金：浙江理工大学科研启动基金(11112932612002)。

摘　　要：为提高抗生素在病灶感染处的渗透与富集能力,减少单一抗生素的使用剂量,降低细菌耐药性的风险,采用化学偶联法合成聚乳酸羟基乙酸-透明质酸的两亲性嵌段共聚物用于封装抗生素。该共聚物在水中可自组装为内部疏水、外部亲水的胶束(Micelles,MS),以透析法将疏水药物环丙沙星(Ciprofloxacin,CIP)和利福平(Rifampicin,RFP)封装在MS中,构建了CIP@MS的单一载药胶束及CIP/RFP@MS的双载药胶束;对合成物质的结构、形貌、临界胶束浓度以及载药率进行测试与表征,将MS、CIP@MS、CIP/RFP@MS与金黄色葡萄球菌(Staphylococcus aureus,S.aureus)和大肠埃希菌(Escherichia coli,E.coli)共培养以探索载药胶束的体外抗菌作用,与人脐静脉内皮细胞共培养以评估载药胶束的体外细胞毒性。结果表明:聚乳酸羟基乙酸-透明质酸聚合物在水中可自组装约为142 nm大小的球形胶束,载药后粒径增大约为194 nm;CIP在CIP@MS中的载药率为1.42%,CIP和RFP在CIP/RFP@MS中的载药率分别为1.09%和1.41%;CIP@MS对S.aureus和E.coli的抗菌率分别为27.7%和99.9%,CIP/RFP@MS对S.aureus和E.coli的抗菌率分别达到85.4%和100.0%。该研究为双载药胶束的制备方法及抗菌方面的应用提供了一定的实验基础和理论依据。To improve the penetration and accumulation ability of antibiotics in treating infected lesions while minimizing dosage of single antibiotics,and reducing the risk of bacterial resistance,an amphiphilic block copolymer comprising poly(lactic acid-co-glycolic acid)and hyaluronic acid was synthesized via chemical conjugation for the encapsulation of antibiotics.This copolymer forms self-assembling micelles(MS)in water,featuring a hydrophobic core and a hydrophobic shell.Hydrophobic drugs,such as ciprofloxacin(CIP)and rifampicin(RFP)were encapsulated within these micelles by using dialysis method,resulting in ciprofloxacin-loaded micelles(CIP@MS)and ciprofloxacin/rifampicin-loaded micelles(CIP/RFP@MS).The synthesized materials were tested and characterized for structure,morphology,critical micelle concentration,and drug loading efficiency.In vitro studies involved co-culturing MS,CIP@MS,and CIP/RFP@MS were co-cultured with Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli)to access antibacterial effects,in as well as evaluating cytotoxicity with human umbilical vein endothelial cells.The results showed that the copolymer of poly(lactic-co-glycolic acid)-hyaluronic acid could self-assemble into uniform spherical micelles in water with a size of approximately 142 nm,increasing to 194 nm post-drug loading.The drug loading efficiency of CIP in CIP@MS was 1.42%,while for in CIP/RFP@MS,it was 1.09%for CIP and 1.41%for RFP,respectively.The antibacterial rates of CIP@MS against S.aureus and E.coli were 27.7%and 99.9%,respectively,while for CIP/RFP@MS,rates reached 85.4%and 100.0%,respectively.This study establishes an experimental basis and theoretical basis for the preparation and the application of dual drug-loaded micelles in antibacterial aspects in some degree.

关 键 词：聚乳酸羟基乙酸 透明质酸 胶束 环丙沙星 利福平 抗菌 

分 类 号：TB324[一般工业技术—材料科学与工程]