氧化石墨烯复合材料载药微球的制备与性能研究  

Preparation and properties of graphene oxide/silk fibroin/rifampicin drug-loading microspheres

作　　者：姜朝瑞 许燕[1] 熊莹 张旭婧[1] Jiang Chaorui;Xu Yan;Xiong Ying;Zhang Xujing(College of Mechanical Engineering,Xinjiang University,Urumqi 830047,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆大学机械工程学院,新疆维吾尔自治区乌鲁木齐市830047

出　　处：《中国组织工程研究》2022年第22期3467-3473,共7页Chinese Journal of Tissue Engineering Research

基　　金：新疆维吾尔自治区科技厅自然科学基金(2017D01C021),项目负责人:许燕。

摘　　要：背景:重度骨结核治愈率低且需要长期服药,但口服药物不良反应大。将载药缓释微球定量置于病灶处不仅可以确保药物浓度和精准治疗,还能有效调控药物释放速度,减少不良反应。目的:优化氧化石墨烯/丝素蛋白/利福平微球的制备工艺。方法:采用乳化法制备氧化石墨烯/丝素蛋白/利福平微球,在确定丝素蛋白浓度3.5%、水油比为1∶6、司盘80与石蜡比1∶10、温度为50℃、利福平与药物载体溶液比50mg∶1mL作为定量的前提下,考察不同搅拌速度(200,500,800 r/min)、不同有机溶剂与水相体积比(1∶1、4∶1、6∶1)及不同氧化石墨烯溶液与丝素溶液溶质比(0.1%,0.25%,0.5%)条件下制备出载药微球的微观形貌、载药率和包封率,确定较佳的制备工艺。结果与结论:(1)扫描电镜显示,500 r/min制备的微球大小均匀,成球性较好;有机溶剂与水相体积比为4∶1制备的微球成球效率较好;氧化石墨烯溶液与丝素溶液溶质比为0.1%制备的微球成球率较高。(2)综合载药率和包封率检测结果,再结合氧化石墨烯/丝素蛋白微球的细胞毒性实验结果,选择在搅拌速度500 r/min、有机溶剂与水相体积比为4∶1、氧化石墨烯溶液与丝素溶液溶质比为0.1%的条件下制备微球,微球的成球率高,载药量为13.5%,包封率为61%,并且该微球在体外可稳定释放药物,在96 h内累计释药量约为67.3%,药物缓控释过程由扩散和溶蚀共同作用。BACKGROUND:The cure rate of severe bone tuberculosis is low and long-term medication is needed,but the adverse reaction of oral drugs is large.Quantitative placement of drug-loaded sustained-release microspheres in lesions can not only ensure drug concentration and precise treatment,but also effectively regulate the rate of drug release and reduce adverse reactions.OBJECTIVE:To optimize the preparation process of graphene oxide/silk fibroin/rifampicin microspheres.METHODS:Graphene oxide/silk fibroin/rifampicin microspheres were prepared by emulsion method.In determining the concentration of silk fibroin 3.5%,water oil ratio 1:6,Span80 and paraffin ratio 1:10,temperature of 50℃,rifampicin and drug carrier solution than 50 mg:1 mL as quantitative premise,the micromorphology,loading rate and encapsulation rate of the drug-loading microspheres were prepared at different stirring speeds(200,500,800 r/min),different organic solvents and water phase volume ratio(1:1,4:1,6:1)and different solute ratios of graphene oxide solution to silk fibroin solution(0.1%,0.25%,0.5%);and the better preparation technology was determined.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the microspheres prepared at 500 r/min were uniform in size and had good pelletforming property.When the volume ratio of organic solvent to water phase was 4:1,the pellet forming efficiency of microspheres was better.When the solute ratio of graphene oxide solution to silk fibroin solution was 0.1%,the pellet formation rate of microspheres was higher.(2)Comprehensive test results of drugloading rate and coating rate,coupled with the graphene oxide/silk fibroin microspheres cytotoxicity experiment result,the microspheres were prepared under the condition of the stirring speed 500 r/min,organic solvent and water phase volume ratio of 4:1,graphene oxide solution and fibroin solution solute ratio of 0.1%.Microsphere formation rate was high;the loading rate was 13.5%;the encapsulation rate was 61%.The microspheres could stably release drugs

关 键 词：氧化石墨烯 丝素蛋白 载药微球 乳化溶剂挥发法 载药量 包封率 累积释药率 释药机制 

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