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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
* 范治平,E-mail: Fanzhiping@lcu.edu.cn;
韩军,E-mail: junhanmail@163.com.
纸质出版日期:2020-02-20,
收稿日期:2019-03-21,
修回日期:2019-11-24,
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范治平, 程萍, 丁壮, 赵燕娜, 李军, 刘敏, Sangeeta Prakash, 张德蒙, 王文丽, 王正平, 韩军. pH 敏感型聚谷氨酸/透明质酸基互穿网络医用水凝胶的制备及表征[J]. 高分子通报, 2020,33(2):23-37.
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(
范治平, 程萍, 丁壮, 赵燕娜, 李军, 刘敏, Sangeeta Prakash, 张德蒙, 王文丽, 王正平, 韩军. pH 敏感型聚谷氨酸/透明质酸基互穿网络医用水凝胶的制备及表征[J]. 高分子通报, 2020,33(2):23-37. DOI: 10.14028/j.cnki.1003-3726.2020.02.004.
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(
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。
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
μ
m
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.
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
Biomedical hydrogelInterpenetrating network hydrogelpH-SensitiveAntibacterialCell 3D culture
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