具有葡萄糖响应性释药的多糖基可注射自愈合水凝胶

谭魏葳; 雷苏苏; 龙涛; 徐志朗; 李德富; 穆畅道; 葛黎明

doi:10.11777/j.issn1000-3304.2023.23024

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具有葡萄糖响应性释药的多糖基可注射自愈合水凝胶

研究论文 | 更新时间：2023-09-25

- 具有葡萄糖响应性释药的多糖基可注射自愈合水凝胶
- Polysaccharide Based Injectable Self-healing Hydrogels with Glucose Responsive Drug Release Behavior
- 高分子学报 2023年54卷第8期页码：1155-1165
- 作者机构：
  
  四川大学化学工程学院制药与生物工程系成都 610065
- 作者简介：
  
  E-mail: geliming@scu.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 22178230);四川省应用基础研究项目(2021YJ0478)
- DOI：10.11777/j.issn1000-3304.2023.23024
  中图分类号：
- 纸质出版日期：2023-08-20，
  
  网络出版日期：2023-05-25，
  
  收稿日期：2023-01-24，
  
  录用日期：2023-03-22
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谭魏葳,雷苏苏,龙涛等.具有葡萄糖响应性释药的多糖基可注射自愈合水凝胶[J].高分子学报,2023,54(08):1155-1165.

Tan Wei-wei,Lei Su-su,Long Tao,et al.Polysaccharide Based Injectable Self-healing Hydrogels with Glucose Responsive Drug Release Behavior[J].ACTA POLYMERICA SINICA,2023,54(08):1155-1165.
谭魏葳,雷苏苏,龙涛等.具有葡萄糖响应性释药的多糖基可注射自愈合水凝胶[J].高分子学报,2023,54(08):1155-1165. DOI： 10.11777/j.issn1000-3304.2023.23024.

Tan Wei-wei,Lei Su-su,Long Tao,et al.Polysaccharide Based Injectable Self-healing Hydrogels with Glucose Responsive Drug Release Behavior[J].ACTA POLYMERICA SINICA,2023,54(08):1155-1165. DOI： 10.11777/j.issn1000-3304.2023.23024.

摘要

葡萄糖响应性自愈合水凝胶能够自发修复结构损伤，并针对高血糖环境快速释放药物，是治疗糖尿病慢性创面的重要策略. 利用自然界储量丰富的天然高分子多糖海藻酸钠、壳聚糖为基材，首先通过高碘酸钠氧化法制备双醛海藻酸钠；对双醛海藻酸钠接枝3-氨基苯硼酸得到苯硼酸-双醛海藻酸钠；苯硼酸-双醛海藻酸钠能够与羧甲基壳聚糖、没食子酸通过动态亚胺键和硼酸酯键形成具有葡萄糖响应性的可注射自愈合水凝胶. 其中，没食子酸既作为交联剂又是治疗糖尿病慢性创面的活性药物. 所制备的多糖基水凝胶呈现出三维多孔结构，具有良好的可注射性、自愈合性、吸水性和机械性能. 有意义的是，水凝胶能够快速响应葡萄糖刺激以快速释放没食子酸. 此外，由于双交联作用形成的水凝胶网络的缓慢崩解，该水凝胶能够持续释放没食子酸. 因此，具有葡萄糖响应以快速-持续释放活性药物的水凝胶在药物递送和糖尿病创面治疗中具有潜在的应用价值.

Abstract

Diabetes mellitus patients commonly suffer from chronic wounds

facing amputation and mortality risk. Hyperglycemia in the diabetic chronic wound environment leads to the hypoxia

immunocytes damage and chronic proinflammatory state

culminating in unhealed wounds. Glucose-responsive self-healing hydrogel

which can repair self-damage spontaneously and release drugs rapidly in the hyperglycemic environment

is an important strategy for chronic diabetic wounds treatment. Herein

a glucose-responsive self-healing hydrogel was prepared based on polysaccharides: sodium alginate was oxidized into dialdehyde sodium alginate by sodium periodate; 3-aminophenylboric acid was grafted onto the chains of dialdehyde sodium alginate; phenylboric acid modified dialdehyde sodium alginate can form self-healing hydrogel (PBA-OSA-CS hydrogel) with carboxymethyl chitosan and gallic acid through dynamic imine bonds and borate ester bonds. Notably

gallic acid is not only a cross-linking agent but also an active drug for treating diabetic chronic wounds. The PBA-OSA-CS hydrogel showed three-dimensional porous structure (30‒60 μm)

good injectability

self-healing properties and mechanical properties (about 22 kPa) and water absorption (about 550%). In-depth exploration revealed that PBA-OSA-CS hydrogel exhibited high sensitivity to glucose stimulation to rapidly release gallic acid. And the double cross-linked network avoided the burst disintegration of hydrogel

contributing to a continuous drug release. The release of gallic acid conformed to the Weibull distribution model (

adj

=0.997

MSC=5.021) and it obeyed the law of Fickian diffusion. Taken together

PBA-OSA-CS hydrogel with glucose response to rapidly and continuously release active drugs has potential applications in drug delivery and diabetes wound treatment.

关键词

水凝胶双醛海藻酸钠壳聚糖葡萄糖响应药物控释

Keywords

HydrogelDialdehyde sodium alginateChitosanGlucose responsivenessDrug controlled release

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