醛基化透明质酸/羟丙基壳聚糖自愈合水凝胶的制备与性能

王艺璇; 曲萌菲; 张杭; 李征征

doi:10.13801/j.cnki.fhclxb.20230207.001

醛基化透明质酸/羟丙基壳聚糖自愈合水凝胶的制备与性能

doi: 10.13801/j.cnki.fhclxb.20230207.001

王艺璇¹,
曲萌菲¹,
张杭¹,
李征征^{1, 2, ,}

1.
天津科技大学　化工与材料学院，天津 300457
2.
复旦大学　聚合物分子工程国家重点实验室，上海200433

基金项目: 天津市海洋资源与化学重点实验室(201706)；2018年度天津市教委科研计划项目(2018KJ110)；天津市制浆造纸重点实验室开放基金资助项目(201809)

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
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出版历程
- 收稿日期: 2022-10-31
- 修回日期: 2023-01-17
- 录用日期: 2023-01-18
- 网络出版日期: 2023-02-08
- 刊出日期: 2023-10-15

Preparation and properties of oxidized hyaluronic acid-hydroxypropyl chitosan self-healing hydrogel

1.
School of Chemical Engineering and Materials, Tianjin University of Science and Technology, Tianjin 300457, China
2.
State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China

Funds: Tianjin Key Laboratory of Marine Resources and Chemistry (201706); 2018 Tianjin Education Commission Scientific Research Program Project (2018KJ110); Tianjin Key Laboratory of Pulp and Paper Open Fund Project (201809)

摘要

摘要: 本文通过使用高碘酸钠将透明质酸(HA)上的羟基氧化为醛基，合成醛基化透明质酸(OHA)。以OHA和羟丙基壳聚糖(HPCS)为原料，通过OHA上的醛基与HPCS的氨基发生席夫碱反应生成动态亚胺键，制备了OHA/HPCS自愈合水凝胶。本文通过使用FTIR、UV-vis、SEM、流变和¹H NMR对OHA/HPCS自愈合水凝胶的微观形貌与性能进行表征与探究。OHA/HPCS水凝胶具有多孔结构，孔径范围在70~200 μm之间。随着OHA用量的增加，OHA/HPCS水凝胶内部的孔隙增多，孔径变小，OHA/HPCS的溶胀比逐渐变小，且降解速率变缓。在室温且无外界刺激的条件下，OHA/HPCS水凝胶在4 h内能够实现自愈合。OHA/HPCS水凝胶能够缓慢释放抗癌药物吉西他滨，药物累计释放率为70%~84%，释放时间为12天。OHA/HPCS水凝胶具有缓慢释放吉西他滨的性能，表明OHA/HPCS水凝胶在药物释放领域具有潜在的应用前景。
- 醛基化透明质酸 /
- 羟丙基壳聚糖 /
- 自愈合 /
- 水凝胶 /
- 药物释放
Abstract: In this paper, oxidized hyaluronic acid (OHA) was synthesized by oxidizing hydroxyl groups on hyaluronic acid (HA) with sodium periodate. OHA/HPCS self-healing hydrogel was prepared by using OHA and hydroxypropyl chitosan (HPCS) as raw materials. The aldehyde group on OHA reacted with the amino group of HPCS to form dynamic imine bond through Schiff base reaction. In this paper, the microscopic morphology and properties of OHA/HPCS self-healing hydrogel was characterized by FTIR, UV-vis, SEM, rheology and ¹H NMR. OHA/HPCS hydrogels have a porous structure, and the results show that the pore size ranged from 70 to 200 μm by changing the amount of OHA. With the increase of the dosage of OHA, the pores in the OHA/HPCS hydrogels increase, the pore size becomes smaller, the swelling ratio of OHA/HPCS becomes smaller, and the degradation rate becomes slower. OHA/HPCS hydrogel can self-heal within 4 h at room temperature without external stimulation. OHA/HPCS hydrogel can release anticancer drug of gemcitabine in sustained way, with a cumulative release percent of 70%-84% in 12 days. OHA/HPCS hydrogels have the properties of sustained release gemcitabine, indicating that OHA/HPCS hydrogels have potential application prospects in the field of drug release.
- oxidized hyaluronic acid /
- hydroxypropyl chitosan /
- self-healing /
- hydrogels /
- sustained drug release

HTML全文

图 1 OHA/HPCS自愈合水凝胶合成路线示意图

Figure 1. Schematic diagram of OHA/HPCS self-healing hydrogels synthesis route

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图 2 透明质酸(HA)和OHA的红外图谱

Figure 2. FTIR spectra of hyaluronic acid (HA) and OHA

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图 3 HPCS、HA、OHA和OHA/HPCS水凝胶的红外图谱

Figure 3. FTIR spectra of HPCS, HA, OHA and OHA/HPCS hydrogels

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图 4 OHA和HA的核磁共振氢谱图

Figure 4. ¹H NMR spectra of OHA and HA

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图 5 OHA₁/HPCS (a)、OHA₂/HPCS (b)和OHA₃/HPCS (c)水凝胶的SEM图像

Figure 5. SEM images of OHA₁/HPCS (a), OHA₂/HPCS (b) and OHA₃/HPCS (c) hydrogels

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图 6 OHA/HPCS水凝胶自愈合图示

Figure 6. Self-healing diagram of OHA/HPCS hydrogels

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图 7 OHA/HPCS 水凝胶的黏弹性能：储能模量G'和损耗模量G''随应变变化曲线

Figure 7. Viscoelastic properties of OHA/HPCS hydrogels: Storage modulus G' and loss modulus G" curves with strain

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图 8 OHA/HPCS自愈合水凝胶的溶胀性能曲线

Figure 8. Swelling performance curves of OHA/HPCS self-healing hydrogels

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图 9 OHA/HPCS水凝胶的体外降解

Figure 9. In vitro degradation of OHA/HPCS hydrogels

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图 10 OHA/HPCS自愈合水凝胶的药物释放曲线

Figure 10. Drug release curves of OHA/HPCS self-healing hydrogels

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表 1 醛基化透明质酸(OHA)/羟丙基壳聚糖(HPCS)水凝胶的实验配比

Table 1. Experimental ratio of oxidized hyaluronic acid (OHA)/hydroxypropyl chitosan (HPCS) hydrogel

Sample OHA/g HPCS/g PBS/mL

OHA₁/HPCS 0.03 0.07 1
OHA₂/HPCS 0.05 0.07 1
OHA₃/HPCS 0.07 0.07 1

Note: PBS—Phosphate buffered saline.

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