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庚酰化乙二醇壳聚糖温敏性水凝胶的制备及其药物缓释

韩晓杰 李征征

韩晓杰, 李征征. 庚酰化乙二醇壳聚糖温敏性水凝胶的制备及其药物缓释[J]. 复合材料学报, 2024, 41(5): 2674-2682. doi: 10.13801/j.cnki.fhclxb.20230825.004
引用本文: 韩晓杰, 李征征. 庚酰化乙二醇壳聚糖温敏性水凝胶的制备及其药物缓释[J]. 复合材料学报, 2024, 41(5): 2674-2682. doi: 10.13801/j.cnki.fhclxb.20230825.004
HAN Xiaojie, LI Zhengzheng. Preparation of heptanoylated glycol chitosan thermo-sensitive hydrogel for sustained drug release[J]. Acta Materiae Compositae Sinica, 2024, 41(5): 2674-2682. doi: 10.13801/j.cnki.fhclxb.20230825.004
Citation: HAN Xiaojie, LI Zhengzheng. Preparation of heptanoylated glycol chitosan thermo-sensitive hydrogel for sustained drug release[J]. Acta Materiae Compositae Sinica, 2024, 41(5): 2674-2682. doi: 10.13801/j.cnki.fhclxb.20230825.004

庚酰化乙二醇壳聚糖温敏性水凝胶的制备及其药物缓释

doi: 10.13801/j.cnki.fhclxb.20230825.004
基金项目: 2018年度天津市教委科研计划项目(2018KJ110);2021年天津市研究生科研创新项目(2021YJSS048)
详细信息
    通讯作者:

    李征征,博士,副研究员,硕士生导师,研究方向为智能高分子水凝胶及其生物医用研究 E-mail: Li.z.z@tust.edu.cn

  • 中图分类号: O63;TB332

Preparation of heptanoylated glycol chitosan thermo-sensitive hydrogel for sustained drug release

Funds: Tianjin Education Commission Scientific Research Program Project (2018KJ110); 2021 Tianjin Graduate Research Innovation Project (2021YJSS048)
  • 摘要: 为了制备一种物理交联的温敏性水凝胶,本文选择水溶性乙二醇壳聚糖(GC)作为基体,通过庚酸酐与GC分子链上的氨基进行酰化反应实现改性,合成了具有不同庚酰度(DS)的庚酰化乙二醇壳聚糖(HAGC)。庚酸酐与GC分子链上氨基的进料摩尔比在0.2~0.25之间,DS介于26.4%~31.5%。通过在GC骨架上引入疏水性庚酰基团,提高GC在有机溶剂中的溶解度和体外生物降解性,而且还引入了温敏性溶胶-凝胶转变性质。HAGC通过分子间相互作用 (氢键和亲疏水相互作用) 发生物理交联,响应环境温度变化而发生溶胶-凝胶相变,通过改变HAGC的DS和溶液浓度,可有效调节HAGC水凝胶的溶胶-凝胶转变温度处于25~37℃之间。HAGC水凝胶具有三维多孔结构,随着DS增加,HAGC水凝胶的交联密度增大、溶胀比降低、药物释放速率减慢。HAGC水凝胶对吉西他滨具有缓释作用,药物释放时间可达5天,药物释放率达到70%~91%。HAGC水凝胶以其优良的温敏性能,在药物注射载体领域具有重要的应用价值。

     

  • 图  1  庚酰化乙二醇壳聚糖 (HAGC)温敏性水凝胶的合成路线示意图

    Figure  1.  Synthetic procedure of heptanoylated glycol chitosan (HAGC) thermo-sensitive hydrogel

    图  2  乙二醇壳聚糖(GC)、HAGC1、HAGC2和HAGC3的FTIR图谱

    Figure  2.  FTIR spectra of glycol chitosan (GC), HAGC1, HAGC2 and HAGC3

    图  3  GC、HAGC1、HAGC2和HAGC3的1H NMR图谱

    Figure  3.  1H NMR spectra of GC, HAGC1, HAGC2 and HAGC3

    图  4  HAGC水凝胶的SEM图像:((a1), (a2)) HAGC1 (3wt%);((b1), (b2)) HAGC2 (3wt%);((c1), (c2)) HAGC3 (3wt%)

    Figure  4.  SEM images of HAGC: ((a1), (a2)) HAGC1 (3wt%); ((b1), (b2)) HAGC2 (3wt%); ((c1), (c2)) HAGC3 (3wt%)

    图  5  试管反转法测定的HAGC的溶胶-凝胶转变相图

    Figure  5.  Sol-gel transition phase diagram of HAGC by the tube inverting method

    图  6  (a) HAGC的溶胶-凝胶转变示意图;(b) HAGC的可逆相变;(c) HAGC的可注射性示意图;(d) 3wt%HAGC3在37℃时呈凝胶状态

    RT—Room temperature

    Figure  6.  (a) Schematic diagram of sol-gel transition of HAGC; (b) Reversible phase transition of HAGC; (c) Injectability diagram of HAGC; (d) Gel form of 3wt%HAGC3 at 37℃

    图  7  HAGCs水凝胶的温度依赖性流变行为:(a) HAGC2 (3wt%); (b) HAGC3 (3wt%); (c) HAGC2 (4wt%);(d) HAGC3 (4wt%)

    T—Temperature; G'—Storage modulus; G"—Loss modulus

    Figure  7.  Temperature dependent rheological behavior of HAGC hydrogels: (a) HAGC2 (3wt%); (b) HAGC3 (3wt%); (c) HAGC2 (4wt%); (d) HAGC3 (4wt%)

    图  8  HAGC1、HAGC2和HAGC3水凝胶的溶胀速率

    Figure  8.  Swelling rate of HAGC1, HAGC2 and HAGC3 hydrogels

    图  9  HAGC水凝胶在溶菌酶溶液中的体外降解

    Figure  9.  Degradation of HAGC hydrogels in lysozyme solution

    图  10  载有吉西他滨的HAGC水凝胶的体外药物释放曲线

    Figure  10.  In vitro drug release profiles of gemcitabine loaded HAGC hydrogels

    表  1  HAGC的合成配比

    Table  1.   Synthetic ratio of HAGC

    SampleMolar ratioaDSb/%Yield/%
    HAGC10.20∶126.486.3
    HAGC20.22∶129.689.9
    HAGC30.24∶131.387.0
    Notes: a—Feed molar ratio of heptanoic anhydride to the amino group of glycol chitosan; b—Degree of heptanoylation determined by the peak integration of 1H NMR; DS—Degree of heptanoylation.
    下载: 导出CSV

    表  2  HAGC水凝胶对吉西他滨的释放机制

    Table  2.   Release characteristics of encapsulated gemcitabine from HAGC hydrogels

    SampleknRelease characteristics
    HAGC10.440.20pseudo-Fickian
    HAGC20.460.23pseudo-Fickian
    HAGC30.510.36pseudo-Fickian
    Notes: k—Rate constant; n—Release index.
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-07-07
  • 修回日期:  2023-08-01
  • 录用日期:  2023-08-12
  • 网络出版日期:  2023-08-28
  • 刊出日期:  2024-05-01

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