盐酸万古霉素@聚乳酸-羟基乙酸共聚物-壳聚糖-透明质酸复合缓释微球的制备及体外评价  

Preparation and in vitro evaluation of vancomycin hydrochloride@polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres

作　　者：乐国平[1] 张明[1] 席立成 罗瀚文 Le Guoping;Zhang Ming;Xi Licheng;Luo Hanwen(Department of Bone Disease and Joint Surgery/Bone Oncology,Fourth Affiliated Hospital of Guangxi Medical University,Liuzhou 545000,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西医科大学第四附属医院骨病关节外科/骨肿瘤科,广西壮族自治区柳州市545000

出　　处：《中国组织工程研究》2022年第4期528-534,共7页Chinese Journal of Tissue Engineering Research

基　　金：广西壮族自治区卫生健康委员会自筹经费科研课题(Z20190244),项目负责人:乐国平。

摘　　要：背景:局部抗生素缓释系统可解决全身应用抗生素时引发的全毒性反应与短期局部注射抗生素半衰期短的问题。目的:制备盐酸万古霉素@聚乳酸-羟基乙酸共聚物-壳聚糖-透明质酸[vaneomyeinhydroehlorid@poly(lactic acid glycolic acid)-chitosanhyaluronic acid,VA@PLGA-CS-HA]复合缓释微球,并对其性能进行评价。方法:采用乳液法制备VA@PLGA-CS-HA复合缓释微球与未载药PLGA-CS-HA复合微球,其中载药微球中万古霉素的质量浓度分别为25,50,100 g/L,检测载药微球的载药量、包封率与体外缓释性能。将3种载药微球分别与金黄色葡萄球菌菌液共培养,相应时间点内检测抑菌率。将4种微球浸提液分别与MC3T3-E1细胞和MG-63细胞共培养,培养1,3,7 d后采用CCK-8法检测细胞毒性。结果与结论:(1)含盐酸万古霉素25,50,100 g/L载药微球的包封率分别为(79.70±5.11)%,(86.41±3.91)%,(63.18±1.96)%,载药量分别为(3.98±0.26)%,(8.64±0.39)%,(12.63±0.39)%;50 g/L载药微球的包封率高于100 g/L载药微球(P<0.05),100 g/L载药微球的载药量高于其他两组(P <0.05);(2)3种载药微球在24 h内均无明显的突释,其中50 g/L载药微球不同时间点的药物释放率快于其他两组,100 g/L载药微球不同时间点的药物释放量高于其他两组,并且3组在56 d时释放的药物质量浓度均高于盐酸万古霉素最小抗菌浓度;(3)3种载药微球均能在一定时间内有效杀死金黄色葡萄球菌,在第14-28天期间3种微球的相对菌落率低于3%,说明3种载药微球能持续而有效杀灭金黄色葡萄球菌;(4)含盐酸万古霉素25,50 g/L载药微球对MC3T3-E1细胞和MG-63细胞无明显的细胞毒性,100 g/L载药微球具有一定的细胞毒性;(5)结果表明,VA@PLGA-CS-HA微球具有良好的缓释性能、抗菌能力与生物组织相容性。BACKGROUND: Local antibiotic slow-release system can solve the problems of total toxicity caused by systemic antibiotics and short half-life of short-term local antibiotics. OBJECTIVE: To prepare polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres loaded with vancomycin and evaluate its performance.METHODS: Vancomycin-loaded polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres and unloaded polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite microspheres were prepared by emulsion method. Mass concentrations of vancomycin in the drug-loaded microspheres were 25, 50, and 100 g/L. The drug-loading amount, encapsulation efficiency, and in vitro sustained release properties of the drug-loaded microspheres were detected. The three kinds of drug-loaded microspheres were co-cultured with Staphylococcus aureus bacteria separately, and the antibacterial rate was detected within the corresponding time points. The four kinds of microsphere extracts were co-cultured with MC3 T3-E1 cells and MG-63 cells, and the cytotoxicity was detected by CCK-8 method after 1, 3, and 7 days of culture. RESULTS AND CONCLUSION:(1) The encapsulation efficiencies of 25, 50, and 100 g/L drug-loaded microspheres were(79.70±5.11)%,(86.41±3.91)%, and(63.18±1.96)%, and the drug loading was(3.98±0.26)%,(8.64±0.39)%, and(12.63±0.39)%. The encapsulation efficiency of 50 g/L drug-loaded microspheres was higher than that of 100 g/L drug-loaded microspheres(P < 0.05). The drug loading of 100 g/L drug-loaded microspheres was higher than that of the other two groups(P < 0.05).(2) Three kinds of drug-loaded microspheres had no obvious burst release within 24 hours, of which the drug release rate of 50 g/L drug-loaded microspheres at different time points was faster than that of the other two groups. The drug release amount of 100 g/L drug-loaded microspheres at different time points was higher than that of the other two groups

关 键 词：骨 材料 微球 盐酸万古霉素 壳聚糖 透明质酸 聚乳酸-羟基乙酸共聚物 生物相容性 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学]