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基于n臂聚乙二醇、聚己内酯和/或甲基丙烯酸的用于控制药物释放的光交联可生物降解水凝胶。

Photo-cross-linked biodegradable hydrogels based on n-arm-poly(ethylene glycol), poly(ε-caprolactone) and/or methacrylic acid for controlled drug release.

作者信息

Hou Ping, Zhang Na, Wu Ruxia, Xu Weiwei, Hou Zhaosheng

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, China.

出版信息

J Biomater Appl. 2017 Oct;32(4):511-523. doi: 10.1177/0885328217730465. Epub 2017 Sep 12.

Abstract

In this paper, a novel kind of photo-cross-linked biodegradable hydrogels based on n-arm-poly(ethylene glycol) ( n = 2, 3, and 4) and poly(ɛ-caprolactone) was prepared by ultraviolet-initiated free radical polymerization. The resulting n-arm-poly(ethylene glycol)-poly(ɛ-caprolactone) and n-arm-poly(ethylene glycol)-poly(ɛ-caprolactone) acrylate (n-arm-PEG-PCL-AC, macromer) were characterized by proton nuclear magnetic resonance and fourier transform infrared spectra. The influences of arm numbers and concentration of macromer on the properties of hydrogel were researched systematically, and the results showed that the gelation time, equilibrium swelling ratio, in vitro degradation, and drug release rate decreased with the increase of arm numbers and concentration of macromer. The degradation and drug release rate could be controlled by varying the cross-linking density of hydrogel, indicating a potential application as controlled drug delivery system. Cytotoxicity test of hydrogel extracts was conducted using L929 mouse fibroblasts, and the relative growth rate exceeded 75% (cytotoxicity type: class 1) after incubation for 24 h, showing excellent cytocompatibility. In addition, the paper presented a pH-sensitive hydrogel (G4) based on 4-arm-PEG-PCL-AC and acrylic acid, and the influences of pH value on swelling behaviors and in vitro drug release of the pH-sensitive hydrogel were examined. The hydrogels shrank under acidic condition and would swell in neutral or basic medium. The pH-dependent drug release behaviors indicated a promising application of the materials as oral drug delivery vehicles.

摘要

本文通过紫外光引发自由基聚合反应制备了一种新型的基于n臂聚乙二醇(n = 2、3和4)与聚己内酯的光交联可生物降解水凝胶。通过质子核磁共振和傅里叶变换红外光谱对所得的n臂聚乙二醇-聚己内酯和n臂聚乙二醇-聚己内酯丙烯酸酯(n臂-PEG-PCL-AC,大分子单体)进行了表征。系统研究了臂数和大分子单体浓度对水凝胶性能的影响,结果表明,随着臂数和大分子单体浓度的增加,凝胶化时间、平衡溶胀率、体外降解率和药物释放速率均降低。通过改变水凝胶的交联密度可以控制降解和药物释放速率,表明其作为药物控释系统具有潜在应用价值。使用L929小鼠成纤维细胞对水凝胶提取物进行了细胞毒性测试,孵育24小时后相对生长率超过75%(细胞毒性类型:1级),显示出优异的细胞相容性。此外,本文还介绍了一种基于4臂-PEG-PCL-AC和丙烯酸的pH敏感水凝胶(G4),并研究了pH值对该pH敏感水凝胶溶胀行为和体外药物释放的影响。水凝胶在酸性条件下收缩,在中性或碱性介质中会膨胀。pH依赖性药物释放行为表明该材料作为口服药物递送载体具有广阔的应用前景。

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