Preparation and Characterization of pH-Sensitive Poly(<italic style="font-style: italic">γ</italic>-glutamic acid)/ Hyaluronic Acid Based Interpenetrating Network Medical Hydrogels

Zhi-ping FAN; Ping CHENG; Zhuang DING; Yan-na ZHAO; Jun LI; Min LIU; Praka-sh SANGEETA; De-meng ZHANG; Wen-li WANG; Zheng-ping WANG; Jun HAN

doi:10.14028/j.cnki.1003-3726.2020.02.004

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Preparation and Characterization of pH-Sensitive Poly(γ-glutamic acid)/ Hyaluronic Acid Based Interpenetrating Network Medical Hydrogels

更新时间：2022-08-31

- Preparation and Characterization of pH-Sensitive Poly(γ-glutamic acid)/ Hyaluronic Acid Based Interpenetrating Network Medical Hydrogels
- Polymer Bulletin Vol. 33, Issue 2, Pages: 23-37(2020)
- 作者机构：
  
  1.聊城大学生物制药研究院,聊城 252059
  2.聊城高新生物技术有限公司,聊城 252059
  3.聊城大学药学院,聊城 252059
  4.昆士兰大学农业与食品科学学院,澳大利亚 4072
  5.海藻活性物质国家重点实验室,青岛 266400
- 作者简介：
- 基金信息：
- DOI：10.14028/j.cnki.1003-3726.2020.02.004
  CLC：
- Published：20 February 2020，
  
  Received：21 March 2019，
  
  Revised：24 November 2019，
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Zhi-ping FAN, Ping CHENG, Zhuang DING, Yan-na ZHAO, Jun LI, Min LIU, Praka-sh SANGEETA, De-meng ZHANG, Wen-li WANG, Zheng-ping WANG, Jun HAN. Preparation and Characterization of pH-Sensitive Poly(γ-glutamic acid)/ Hyaluronic Acid Based Interpenetrating Network Medical Hydrogels. [J]. Polymer Bulletin 33(2):23-37(2020)
DOI：

Zhi-ping FAN, Ping CHENG, Zhuang DING, Yan-na ZHAO, Jun LI, Min LIU, Praka-sh SANGEETA, De-meng ZHANG, Wen-li WANG, Zheng-ping WANG, Jun HAN. Preparation and Characterization of pH-Sensitive Poly(γ-glutamic acid)/ Hyaluronic Acid Based Interpenetrating Network Medical Hydrogels. [J]. Polymer Bulletin 33(2):23-37(2020) DOI： 10.14028/j.cnki.1003-3726.2020.02.004.

摘要

生物材料是推动生物医学领域日新月异变化的基石

医用水凝胶作为重要成员

近年来表现出蓬勃发展的态势。文章介绍了一种新型可注射的、以生物相容性方法交联的聚谷氨酸(Poly (γ-glutamic acid)

PGA)/透明质酸(Hyaluronic acid

HA)复合水凝胶。研究首先采用 EDC/NHS方法合成了酪胺(Tyramine

Ty)接枝聚谷氨酸的PGA-Ty前体大分子及半胱胺(Cysteamine

CA)修饰透明质酸的HA-CA 前体大分子。两种前体大分子的结构分别使用核磁和红外进行了确证。得到的两种前体大分子在低浓度双氧水和辣根过氧化物酶(Horseradish Peroxidase

HRP)的共同作用下

于水相中交联得到互穿网络(Interpenetrating Network

IPN)水凝胶。实验对IPN水凝胶样品的系列性能

如平衡含水量、内部形貌、酶降解速率以及力学性能等进行了测试

并选取了盐酸四环素为药物模型对凝胶的体外药物释放行为、体外抗菌效果进行了测评。凝胶材料的细胞毒性及凝胶支架对细胞3D培养的效果证明其生物相容性优异

体外包埋的细胞经72h培养

未表现出明显细胞毒性。系列数据证明

该种水凝胶可以设计成为pH 敏感型的药物控释载体材料

并因其良好的生物相容性

也有作为细胞支架、创伤辅料等其它生物医用材料的潜力。

Abstract

Biomaterials are the cornerstone to promote the rapid changes in the field of biomedicine. Biohydrogel

as an important member

has shown a vigorous development trend in recent years. A new injectable poly(γ-glutamic) acid (PGA)/hyaluronic acid (HA) composite hydrogel crosslinked by biocompatible method was introduced in this study. Firstly

the PGA-Ty precursor and the HA-CA precursor were synthesized by EDC/NHS protocol. The structures of both precursors were confirmed by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). The two precursors were crosslinked in aqueous phase under the combined action of low concentration hydrogen peroxide (10 mM) and horseradish peroxidase (HRP

10U·mL

-1

) to obtain interpenetrating network (IPN) hydrogels. The properties of series IPN hydrogels

such as equilibrium water content

morphology

enzymatic degradation profile and mechanical properties were tested. Mechanical strength of I3 and I3' hydrogels were 8113Pa and 9629Pa

respectively. Equilibrium water content could be varied from 13.3~21. Porous scaffolds

whose pore size of internal structure was in the range of 10~100

could be obtained after IPN hydrogel be lyophilized. The drug release behavior and antibacterial effect

in vitro

were evaluated by using tetracycline hydrochloride as a drug model. Under physiological conditions

both of the drug loaded hydrogels showed regular drug release profiles and a certain pH sensitivity. After 5 days release

the cumulative release rate of the drug was 77.74%

while the drug loaded hydrogel in acidic environment had released 92%. The cytotoxicity of gel materials and the effect of cell 3D culture showed that its biocompatibility was good. The cells embedded

in vitro

did not show obvious cytotoxicity through 72h culture. Series of data show that these IPN hydrogels can be designed as a pHsensitive drug delivery carrier. And because of its good biocompatibility

it also has potential as a cell scaffold

trauma excipient or other biomedical materials.

关键词

生物医用水凝胶互穿网络水凝胶pH 敏感型抗菌细胞3D培养

Keywords

Biomedical hydrogelInterpenetrating network hydrogelpH-SensitiveAntibacterialCell 3D culture

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Related Author

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Related Institution

College of Chemistry and Chemical Engineering, Shaanxi University of Science & Technology

Key Laboratory of Chemical Additives for China National Light Industry

College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology

Xi’an Key Laboratory of Advanced Performance Materials and Polymers, Shaanxi University of Science and Technology

Qingdao Innovation and Development Center of Harbin Engineering University, Key Laboratory of Superlight Material and Surface Technology of Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University

⁰

Preparation and Characterization of pH-Sensitive Poly(γ-glutamic acid)/ Hyaluronic Acid Based Interpenetrating Network Medical Hydrogels

DOI：10.14028/j.cnki.1003-3726.2020.02.004

摘要

Abstract

关键词

Keywords

references