中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (10): 1515-1521.doi: 10.12307.2022.197

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

负载利福平丝素蛋白微球的制备及性能

安田田，许  燕，陈慧明，张旭婧，谭  浩   

  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
  • 收稿日期:2020-08-11 修回日期:2020-08-12 接受日期:2020-09-19 出版日期:2022-04-08 发布日期:2021-10-25
  • 通讯作者: 许燕，教授，博士生导师，新疆大学机械工程学院，新疆维吾尔自治区乌鲁木齐市 830047
  • 作者简介:安田田，女，1995年生，新疆维吾尔自治区石河子市人，硕士，主要从事组织工程骨支架制备与性能研究
  • 基金资助:
    新疆维吾尔自治区自然科学基金资助项目(2017D01C021)，项目负责人：许燕

Preparation and performance of rifampicin-silk fibroin microspheres

An Tiantian, Xu Yan, Chen Huiming, Zhang Xujing, Tan Hao   

  1. College of Mechanical Engineering, Xinjiang University, Urumqi 830047, Xinjiang Uygur Autonomous Region, China
  • Received:2020-08-11 Revised:2020-08-12 Accepted:2020-09-19 Online:2022-04-08 Published:2021-10-25
  • Contact: Xu Yan, Professor, Doctoral supervisor, College of Mechanical Engineering, Xinjiang University, Urumqi 830047, Xinjiang Uygur Autonomous Region, China
  • About author:An Tiantian, Master, College of Mechanical Engineering, Xinjiang University, Urumqi 830047, Xinjiang Uygur Autonomous Region, China
  • Supported by:
    the Natural Science Foundation of Xinjiang Uygur Autonomous Region, No. 2017D01C021 (to XY) 

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摘要：

文题释义：

丝素蛋白：是从蚕丝中提取的天然高分子材料，含有18种氨基酸，二级分子结构主要为α-螺旋、β-折叠、β-转角和无规卷曲，形成2种不同的晶体构象方式SilkⅠ和SilkⅡ， SilkⅠ主要是α-螺旋、β-转交和无规卷曲结构，Silk Ⅱ主要是β-折叠结构，两种形态在一定外界条件下可相互转换，进而可调节丝素蛋白的降解性能和机械性能，具有优异的生物相容性、可控的生物降解性和良好的机械性，可作为仿生材料与生物医用材料。
载药微球：是通过天然或合成的生物材料作为药物的媒介或载体，采用物理或化学方法将药物包覆在基材中，在一定条件下载体材料中包埋的生物活性药物可通过扩散及基材的降解等途径释放出来。

背景：目前治疗骨关节结核最常选择的方案是口服和全身应用抗结核药物，但易产生耐药结核菌株和药物不良反应，病灶处局部药物浓度较低。可降解载药微球置埋在病灶处能够定点给药，延缓药物释放并控制释药速率，对治疗骨关节结核提供一种新的治疗手段。
目的：设计正交实验对负载利福平丝素蛋白载药微球的制备工艺参数进行优化，制备出形貌圆整、粒径均匀、载药率和包封率高的缓释微球，并探究微球体外药物释放行为。
方法：以丝素蛋白溶液为水相、液体石蜡为油相、司盘80为乳化剂，采用乳化溶剂挥发法制备出负载利福平的丝素蛋白微球。设计正交实验考察搅拌转速(300，500，700，900 r/min)、异丙醇与丝素蛋白溶液体积比(1∶1，2∶1，4∶1，6∶1)、水油体积比(1∶6，1∶8，1∶10，1∶12)、乳化剂含量(2%，4%，6%，8%)及温度(25，35，45，55 ℃)对载药微球粒径、载药率和包封率的影响。
结果与结论：正交实验结果显示，最佳载药微球制备工艺为：搅拌转速为900 r/min，异丙醇与丝素蛋白溶液体积比为1∶1，水油体积比为1∶6，司盘80浓度为2%，温度为55 ℃。在此条件下制备的微球表面光滑圆整，成球效果好，微球粒径约为11.18 µm，载药量为10.56%，包封率为42.78%，在144 h内累计释药率为68.4%，释药速率持续平稳，具有良好的药物缓释性能。

https://orcid.org/0000-0002-8352-3987 (安田田)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 材料, 丝素蛋白, 微球, 载药微球, 正交实验, 乳化溶剂蒸发法, 载药率, 包封率, 累积释药率, 缓释

Abstract: BACKGROUND: At present, the most common choice for treatment of bone joint tuberculosis is oral and systemic anti-tuberculosis drugs, but drug-resistant tuberculosis strains and drug side effects are prone to occur, and the local drug concentration is low at the lesion. Biodegradable microspheres buried in the lesions can be given at a specific point, delay drug release and control the rate of release, providing a new treatment for the treatment of bone joint tuberculosis.
OBJECTIVE: To design orthogonal experiments to optimize the preparation process parameters of rifampicin-loaded silk fibroin microspheres, and prepare sustained-release microspheres with round morphology, uniform particle size, high drug loading and encapsulation rates, and to explore the release behavior of the microsphere in vitro drug experiment.
METHODS: Using silk fibroin solution as the water phase, liquid paraffin as the oil phase, and Span-80 as the emulsifier, the silk fibroin drug-loaded microspheres loaded with rifampicin were prepared by the emulsification solvent positive method. Orthogonal experiment was designed to investigate stirring speed (300, 500, 700, 900 r/min), isopropanol and silk fibroin solution volume ratio (1:1, 2:1, 4:1, 6:1), water-oil volume ratio (1:6, 1:8, 1:10, 1:12), emulsifier content (2%, 4%, 6%, 8%) and temperature (25, 35, 45, 55 °C) influences on the morphology, drug loading rate and encapsulation rate of drug-loaded microspheres. 
RESULTS AND CONCLUSION: Orthogonal experiment results showed that the best process parameters were the stirring speed of 900 r/min, the volume ratio of isopropanol to silk fibroin solution of 1:1, the volume ratio of water to oil of 1:6, the Span-80 concentration of 2%, and the temperature of 55 °C. Under this condition to make silk fibroin microspheres, the surface of the microsphere was smooth, with good spherical effect; the microsphere size was about 11.18 µm; drug-loaded rate was 10.56%; encapsulated rate was 42.78%; cumulative release rate of 68.4% in 144 hours. Microsphere is stable and sustained on drug release, and has a good drug release effect.

Key words: material, silk fibroin, microsphere, drug-loaded microsphere, orthogonal experiment, emulsification solvent evaporation method, drug-loaded rate, encapsulation rate, cumulative drug release rate, sustained release

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