纺织学报 ›› 2021, Vol. 42 ›› Issue (10): 180-189.doi: 10.13475/j.fzxb.20200702810

• 综合述评 • 上一篇    下一篇

高分子聚合物栓塞微球的研究进展

李枫1, 杨嘉豪1, 赖耿昌1, 王建南1,2, 许建梅1,2()   

  1. 1.苏州大学 纺织与服装工程学院, 江苏 苏州 215021
    2.苏州大学 纺织行业医疗健康用蚕丝制品重点实验室, 江苏 苏州 215127
  • 收稿日期:2020-07-13 修回日期:2021-01-20 出版日期:2021-10-15 发布日期:2021-10-29
  • 通讯作者: 许建梅
  • 作者简介:李枫(1995—),女,硕士生。主要研究方向为栓塞微球的制备。
  • 基金资助:
    中国纺织工业联合会科技指导性项目(2018023);苏州大学大学生创新创业训练计划(202010285113Y)

Research progress of polymer embolic microspheres

LI Feng1, YANG Jiahao1, LAI Gengchang1, WANG Jiannan1,2, XU Jianmei1,2()   

  1. 1. College of Textile and Clothing Engineering, Soochow University, Suzhou, Jiangsu 215021, China
    2. Key Laboratory of Silk Products for Medical and Health Use in Textile Industry, Soochow University, Suzhou, Jiangsu 215127, China
  • Received:2020-07-13 Revised:2021-01-20 Published:2021-10-15 Online:2021-10-29
  • Contact: XU Jianmei

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摘要：

为促进高分子聚合物栓塞微球向更高载药率、药物可控释、多功能化方向发展,综述了栓塞微球的作用机制,以及壳聚糖、海藻酸盐等高分子聚合物作为药物载体材料的制备特性;介绍了乳化交联法、离子凝胶法等栓塞微球制备技术,装载水溶性、脂溶性等药物的载药微球的制备特点。最后指出选择合适的载体材料或者多种材料复合的方式可提高微球载药率,使得药物可控释放,根据所负载药物的特性选择合适的微球制备方法可实现高载药率。认为未来栓塞微球的研究应向多功能化方向发展,如负载靶向化疗药的微球、具有靶向性的微球、缓解栓塞疼痛感或癌痛的微球、具有光热效应的微球、降解速度可控的微球等,可为促进栓塞微球在治疗肿瘤方面的研究与应用提供参考。

关键词: 栓塞微球, 动脉化疗栓塞术, 生物相容性, 载药微球, 微流控技术

Abstract:

In order to promote the embolic polymer microspheres towards the direction of a higher drug-loading rate, controlled drug release, functionalization. Mechanism of embolic microspheres were reviewed, as well as the application of the polymer such as chitosan and alginate in the drug microspheres preparation. The embolic microsphere preparation methods such as emulsification cross-linking method, and ionic gelation method were introduced, as well as the different preparation characteristics of drug loaded microspheres for water-soluble and lipid-soluble drugs. Finally it is pointed out that the drug loading rate of the microspheres can be improved by selecting suitable carrier materials or multiple composite materials, so that the drug can be released in a controlled manner; suitable preparation methods of microspheres were selected to achieve high drug loading rate according to the characteristics of the loaded drugs; the future studies on embolic microspheres should be developed in the direction of multifunctionalization, such as microspheres with load targeted chemotherapy drugs, microspheres with targeting properties, microspheres that alleviate embolic pain or cancer pain, microspheres with photothermal effect, microspheres with controllable degradation rate, etc., providing reference and support for promoting the research and application of embolic microspheres in the treatment of tumors.

Key words: embolic microsphere, trancatheter arterial embolization, biocompatibility, drug loaded microsphere, microfluidic technique

中图分类号: 

  • TS101.4

表1

高分子聚合物栓塞微球的研究状况"

材料 药物 方法 粒径外形 交联剂 包封率
(载药率)/
%		 研究结果
壳聚糖(CS) 5-FU 离子凝胶法 空白微球:30~60 nm,包封后粒径变大。圆形,光滑 多聚磷酸钠
(TPP)		 — 微球分散性和稳定性好,粒径分布均一,缓释时间可达120 h[2]
平均6.40 μm,大小均一 77.80 对药物包封率高,突释小[3]
盐酸四环素 乳化交联法 5~50 μm,球形,表面光滑 甲醛/戊二醛 56.30
(26.90)		 复合交联剂制备微球缓释性更好[4]
盐酸阿霉素 普通微球80.79 μm;高乙酰化微球81.25 μm。均为球形 — — 高乙酰化微球载药率更高[16]
白藜芦醇 53~311 μm,表面光滑,颗粒不规则,内部有空隙 香草素 93.68 可使用多酚类化合物作为无毒交联剂[17]
罗素蝰蛇霉素 离子交联法 30~60 nm,球形 TPP — TPP交联,分布均匀,离散性好[18]
牛至挥发油 离子凝胶/
乳化交联法		 40~80 nm,球形,规则分布 TPP — 空白微球比载药微球尺寸小,因团聚和溶胀,部分载药微球尺寸达到309~402 nm[19]
牛血清蛋白 膜乳化法 最小粒径0.40 μm 戊二醛/甲苯 — 微球的大小分布均匀[20]
西咪/法莫 喷雾干燥法 4~5 μm,光滑球形但变形 戊二醛/甲醛 — 药物释放快,并伴有爆释[21]
超顺磁性纳米粒 超声化学法 球形 — — 微球可被检测到[22]
CS/丝素蛋白 牛血清白蛋白 乳化交联法 7.84 μm左右,规则光滑 京平尼 50.16
(1.25)		 减少初期爆释,延长缓释时间 [ 7 ]
CS/Fe3O4 大约40 μm,规则球形 — — 用作放射性核素靶向载体[23]
海藻酸钠 儿茶素 乳液凝胶法 — — 41.48 用油性乳液凝胶法缓释效果更好[24]
CS/海藻酸钠 顺铂 乳化交联法 11.00 μm,球形规整 — 77.28
(19.93)		 初期爆释减少,延长释放时间[25]
茶多酚 反相乳液法 500 nm左右,球形度较好 — 61.38
(22.71)		 微球粒径均匀[26]
明胶/CS 茶多酚 自组装 规则球形,表面光滑 — 90.42
(26.82)		 过程绿色,温和,简便[8]
阿司匹林 乳化交联法 球形规整圆滑 戊二醛 — 更有利于微球的圆滑和刚性[9]
酪蛋白磷酸肽/CS (+)-表没食子
儿茶素-3-没食
子酸酯		 自组装 — — — 用于口服时,提高药物在肠道通透性和吸收能力[27]
磷脂酰胆碱/胆固醇 绿茶多酚 — — — — 作为口服给药时提高药物稳定性和生物利用度,实现药物的缓释[28]
聚乙烯醇 — 微流控技术 均匀粒径,纳米结构 — — 方法简单,经济,可行,双模成像[29]
聚丙烯酸 — 原位沉淀法 球形,表面光滑 — — 微球可被灵敏检测到[30]
利多卡因 — 圆形,表面光滑 — — 缓解栓塞引起的疼痛[15]
明胶 阿霉素 反相悬浮法 180~350 μm规则球形 — — 突释小 [ 5 ]
— — 多酚、京平尼 — 多酚交联剂优于京平尼且成本低 [ 6 ]
海藻酸钙 凝血酶 静电液滴 — — — 治疗引起的炎症随微球降解消失[31]
淀粉 阿霉素 乳液凝胶法 —
10~90 μm,表面多孔,不规则		 — — 用于晚期患者中也安全[32]
二氧化钛 — — 多孔二氧化钛微球具有高载药量[33]

图1

硫化铋纳米粒子微球的制备工艺"

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