基于席夫碱键的可注射糖肽水凝胶的制备及性能

doi:10.7503/cjcu20160088

高等学校化学学报 ›› 2016, Vol. 37 ›› Issue (9): 1750.doi: 10.7503/cjcu20160088

• 高分子化学 • 上一篇

基于席夫碱键的可注射糖肽水凝胶的制备及性能

赵麒^1,², 何婉莹¹, 段莉洁¹(), 张瑜², 于双江², 高光辉¹

1. 长春工业大学化学工程学院高分子化学与物理系, 长春 130012
2. 中国科学院长春应用化学研究所, 生态环境高分子材料重点实验室, 长春 130022

收稿日期:2016-02-02 出版日期:2016-09-10 发布日期:2016-08-26
作者简介:联系人简介: 段莉洁, 女, 博士, 副教授, 主要从事生物医用高分子材料研究. E-mail:duanlijie@ccut.edu.cn
基金资助:
国家自然科学基金(批准号: 21204081)资助

Fabrication and Characterization of Injectable Polysaccharide-polypeptide Hydrogel Based on Schiff’s Base^†

ZHAO Qi^1,², HE Wanying¹, DUAN Lijie^1,^*(), ZHANG Yu², YU Shuangjiang², GAO Guanghui¹

1. Department of Polymer Chemistry and Physics, School of Chemical Engineering,Changchun University of Technology, Changchun 130012, China
2. Key Laboratory of Polymer Eco-materials, Changchun Institute of Applied Chemistry,Chinese Academy of Sciences, Changchun 130022, China

Received:2016-02-02 Online:2016-09-10 Published:2016-08-26
Contact: DUAN Lijie E-mail:duanlijie@ccut.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(No.21204081)

摘要/Abstract

摘要：

以氧化葡聚糖(ODEX)和聚赖氨酸-聚乙二醇-聚赖氨酸(PLL₂₄-PEG-PLL₂₅)三嵌段聚合物为前驱体, 通过ODEX中的醛基与PLL中的氨基之间的席夫碱键反应, 制备了ODEX/PLL₂₄-PEG-PLL₂₅水凝胶. 研究了其凝胶强度、降解时间及对阿霉素(DOX)释放量的影响. 结果表明, 随着ODEX中醛基密度的增加, 凝胶强度逐渐增大, 最大强度为3100 Pa. 流变学研究结果表明, 由于ODEX中的醛基与DOX中的氨基存在席夫碱键作用, 导致凝胶强度从2160 Pa降至1730 Pa. 降解实验结果表明, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶具有较长的降解时间, 最长时间达到29 d. 药物释放结果表明, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶具有酶促降解释放药物的性能. 在Elastase溶液中, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶所载DOX累积释放量达到最大值74.35%. 结果表明, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶具有进一步应用于体内局部药物传输的潜力.

关键词: 氧化葡聚糖, 聚赖氨酸, 酶响应, 可注射糖肽水凝胶, 控制释放, 席夫碱

Abstract:

The purpose of gel is applied to body with no toxic. Based on dextran, oxidized dextran(ODEX) with the different oxidation extent was prepared. At the same time, the tri-block polymers poly(lysine)-polyethylene glycol-poly(lysine)(PLL₂₄-PEG-PLL₂₅) was synthesized, which becomes hydrogels through the reaction between the dextran aldehyde groups and the poly-L-lysine amino groups via Schiff’s base formation. The storage modulus, degradation time of gel, and release of doxorubicin(DOX) were characterized. The results showed that gel strength increased gradually with the increasing density of aldehyde in ODEX, and the maximum storage modulus was 3100 Pa. The rheological test indicates that the storage modulus was reduced from 2160 Pa to 1730 Pa, due to the Schiff’s effect between ODEX aldehyde group and DOX amine group. The gel had a long degradation time up to 29 d. Drug release studies showed that DOX released from carrier gel was triggered by the enzyme. In Elastase solution, DOX release rate had reached up to 74.35%. The findings reveal that the hydrogel have promising applications in drug delivery in vivo.

Key words: Oxidized dextran, Polylysine, Enzyme response, Injectable polysaccharide-polypeptide hydrogel, Controlled release, Schiff’s base

TrendMD:

赵麒, 何婉莹, 段莉洁, 张瑜, 于双江, 高光辉. 基于席夫碱键的可注射糖肽水凝胶的制备及性能. 高等学校化学学报, 2016, 37(9): 1750.

ZHAO Qi, HE Wanying, DUAN Lijie, ZHANG Yu, YU Shuangjiang, GAO Guanghui. Fabrication and Characterization of Injectable Polysaccharide-polypeptide Hydrogel Based on Schiff’s Base^†. Chem. J. Chinese Universities, 2016, 37(9): 1750.

图/表 10

Scheme 1 Synthesis routes of PLL24-PEG2000-PLL25 and ODEX

Fig.1 1H NMR of PLL24-PEG-PLL25

Fig.2 1H NMR of ODEX

Fig.3 FTIR spectra of ODEX(a) and ODEX/PLL24-PEG-PLL25(b)

Scheme 2 Formation graphic statement of PLL24-PEG-PLL25/ODEX hydrogels

Fig.4 SEM images of Gel 3(A, C) and Gel 3+DOX(B, D)

Fig.5 Storage modulus G' of gels a. Gel 1; b. gel 2; c. gel 3.

Fig.6 Storage modulus G'(a, b) and loss modulus G″(c, d) of Gel 3(a, c) and Gel 3+DOX(b, d)

Fig.7 In vitro degradation test of Gel 3+DOX hydrogels carried out with PBS(a) and Elastase(b) at 37 ℃

Fig.8 Release profile of Gel 3+DOX from Elastase(a), Proteinase K(b), PBS(c) at 37 ℃ over 21 d

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基于席夫碱键的可注射糖肽水凝胶的制备及性能

Fabrication and Characterization of Injectable Polysaccharide-polypeptide Hydrogel Based on Schiff’s Base^†

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基于席夫碱键的可注射糖肽水凝胶的制备及性能

Fabrication and Characterization of Injectable Polysaccharide-polypeptide Hydrogel Based on Schiff’s Base†

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Fabrication and Characterization of Injectable Polysaccharide-polypeptide Hydrogel Based on Schiff’s Base^†