纺织学报 ›› 2025, Vol. 46 ›› Issue (05): 116-124.doi: 10.13475/j.fzxb.20240700101

• 纤维材料 • 上一篇    下一篇

丝素/壳聚糖/明胶栓塞微球的制备及其降解性能

李鹏飞1, 罗忆心1, 张子凡1, 陆宁1, 陈碧泠1, 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 江苏省纺织印染节能减排与清洁生产工程研究中心, 江苏 苏州 215127
  • 收稿日期:2024-07-01 修回日期:2025-02-08 出版日期:2025-05-15 发布日期:2025-06-18
  • 通讯作者: 许建梅(1976—),女,副教授,博士。主要研究方向为生物材料。E-mail:xujianmei@suda.edu.cn。
  • 作者简介:李鹏飞(1999—),男,硕士生。主要研究方向为栓塞微球的制备。
  • 基金资助:
    纺织行业医疗健康用蚕丝制品重点实验室项目(Q811580321)

Preparation and degradation performance of silk fibroin/chitosan/gelatin embolic microspheres

LI Pengfei1, LUO Yixin1, ZHANG Zifan1, LU Ning1, CHEN Biling1, XU Jianmei1,2()   

  1. 1. College of Textile and Clothing Engineering, Soochow University, Suzhou, Jiangsu 215021, China
    2. Jiangsu Engineering Research Center of Textile Dyeing and Printing for Energy Conservation, Discharge Reduction and Cleaner Production, Soochow University, Suzhou, Jiangsu 215127, China
  • Received:2024-07-01 Revised:2025-02-08 Published:2025-05-15 Online:2025-06-18

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摘要：

为实现栓塞微球降解行为的可控设计,采用离子凝胶法与乳化交联法联用,利用具有不同降解速度和特性的丝素蛋白(SF)、壳聚糖(CS)、明胶(GEL)材料以不同配比复合制备栓塞微球。经正交试验探究了SF与CS质量比分别为9:1、7:3、5:5时栓塞微球的最优制备工艺条件,并在此基础上利用配方设计中的极端顶点法设计并制备了不同配比的SF/CS/GEL栓塞微球,对栓塞微球的外观形貌、化学组成、热稳定性、降解性能进行了表征。结果表明:在丝素蛋白与壳聚糖不同配比下均可以通过正交试验获得较大尺寸栓塞微球(微球粒径为200~400 μm和550~750 μm)的最优制备工艺条件,制得球形圆整、分散性好的微球;微球中3种材料之间存在氢键、席夫碱等相互作用;获得不同组分配方在3种降解酶体系(蛋白酶ⅩⅣ、溶菌酶或2种酶联用)中的降解率回归方程,拟合优度显著,可实现对不同配方栓塞微球降解性能的预测与设计。

关键词: 医用栓塞材料, 栓塞微球, 丝素, 壳聚糖, 明胶, 降解性能

Abstract:

Objective Embolic microspheres with varying degradation rates are better suited for personalized treatment protocols, considering different tumor types, stages, and treatment approaches. In order to achieve controlled degradation in embolic microspheres, the distinct degradation properties of silk fibroin, chitosan, and gelatin were utilized to design and fabricate microspheres with precise degradation profiles and rates.
Method Embolic microspheres were prepared using a two-step emulsification method. The extreme vertex method in material mixing design was employed to obtain silk fibroin/chitosan/gelatin (SF/CS/GEL) microspheres with varying component ratios. Regression equations were established, and mixed contour maps were drawn to reflect the specific degradation mass residual rate of the microsphere components in the presence of different enzymes after 21 d.
Results The photos of embolic microspheres from three orthogonal experiments were utilized to assess the roundness and adhesion levels, and the results were subjected to analysis of variance so as to determine the optimal process conditions. SEM images showed that the SF/CS microspheres had a porous surface while retaining a generally spherical shape. The SF/CS/GEL microspheres exhibited improved roundness, with smoother surfaces and smaller pore sizes as the gelatin content increased. Infrared spectroscopy analysis demonstrated that the silk fibroin structure transformed from random coiling to β-pleated sheets during microsphere formation. The aldehyde groups of glutaraldehyde reacted with amino groups on silk fibroin, chitosan, and gelatin, forming Schiff bases, with significant hydrogen bonding interactions observed between the three matrix materials. Thermogravimetric analysis indicated that the thermal stability of SF/CS and SF/CS/GEL microspheres significantly surpassed that of the individual materials, suggesting structural changes due to crosslinking agents during microsphere formation. Regression analysis was performed on the mass residual rate of the microspheres after 21 d of degradation in relation to the proportions of silk fibroin, chitosan, and gelatin, resulting in a fitted regression equation. The mixed contour map of mass residual rates was adopted to analyze the trends in the mass residual rates of microspheres after 21 d of degradation, correlating with varying component proportions.
Conclusion Optimal preparation conditions were determined through orthogonal experiments with varying ratios of silk fibroin and chitosan, resulting in spherical, round, and well-dispersed microspheres. The regression equations for degradation rates of various formulations across three enzyme systems exhibited significant goodness of fit, enabling the prediction and design of degradation performance for embolic microspheres with different ratios. This approach offers a method and theoretical foundation for achieving controlled degradation of embolic microspheres.

Key words: embolic material, embolic microsphere, silk fibroin, chitosan, gelatin, degradation performance

中图分类号: 

  • TS101.4

图1

丝素蛋白/壳聚糖栓塞微球的制备工艺流程"

表1

正交试验因素水平值"

SF与CS
质量比		 水平 A
油水比		 B
乳化剂体积
分数/%		 C
戊二醛体积
分数/%
9:1 1 3:2 0.92 4.0
2 7:4 0.96 4.4
3 2:1 1.00 4.8
7:3 1 3:2 0.92 3.6
2 7:4 0.96 3.8
3 2:1 1.00 4.0
5:5 1 3:2 0.92 2.4
2 7:4 0.96 3.0
3 2:1 1.00 3.6

图2

极端顶点法设计试验点示意图"

表2

各组分材料的质量分数(极端顶点法设计)"

水平
数		 SF质量
分数(x1)/
%		 CS质量
分数(x2)/
%		 GEL质量
分数(x3)/
%		 微球
命名
1 50.00 50.00 0 MS1
2 61.25 16.25 22.50 MS2
3 54.75 37.75 7.50 MS3
4 63.00 7.00 30.00 MS4
5 90.00 10.00 0 MS5
6 35.00 35.00 30.00 MS6
7 47.25 30.25 22.50 MS7
8 74.75 17.75 7.50 MS8
9 59.50 25.50 15.00 MS9

图3

不同试验条件下制备的微球照片"

图4

SF/CS、SF/CS/GEL微球(550~750 μm)的SEM照片"

图5

SF/CS与SF/CS/GEL微球(200~400 μm)的SEM照片"

图6

SF、CS、GEL和不同组分微球的红外光谱"

图7

SF、CS、GEL、SF/CS、SF/CS/GEL微球的热重分析"

表3

不同组分配方微球的降解质量残留率"

微球尺
寸规格/μm		 试验号 21 d时的降解质量残留率/%
蛋白酶ⅩⅣ组 溶菌酶组 2种酶联用组
550~750 1 92.47±1.14 68.93±3.07 65.33±3.21
2 74.53±3.01 79.47±2.76 69.93±2.61
3 88.20±8.55 73.67±7.29 73.40±2.23
4 76.27±3.53 80.20±3.83 67.67±1.03
5 84.93±11.72 95.47±0.64 86.67±5.74
6 85.40±9.01 62.47±6.70 60.33±7.40
7 89.73±0.31 69.47±3.70 67.13±2.16
8 84.00±4.06 85.87±8.04 79.60±1.25
9 82.00±4.13 76.47±4.15 74.07±2.70
200~400 1 90.07±0.58 66.40±1.74 62.87±7.33
2 76.87±2.10 76.20±11.81 68.53±1.53
3 85.60±3.27 72.13±6.90 70.73±3.61
4 69.40±8.66 79.53±2.73 65.33±1.45
5 81.30±6.20 94.40±2.75 85.47±4.61
6 80.30±4.44 59.67±3.40 58.67±3.69
7 83.20±0.92 67.47±1.20 65.80±1.25
8 81.07±1.67 84.47±2.50 78.80±7.63
9 80.87±6.09 76.27±3.70 71.87±4.41

图8

不同酶作用下不同组分配比微球在21 d后的降解质量残留率的混合等值线图"

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