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藻酸盐基刺激响应型、非细胞毒性、三元共聚半互穿网络水凝胶的制备及其作为牛血清白蛋白和 5-氨基水杨酸控制释放载体。

Fabrication of alginate-based stimuli-responsive, non-cytotoxic, terpolymric semi-IPN hydrogel as a carrier for controlled release of bovine albumin serum and 5-amino salicylic acid.

机构信息

Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea; Convergence Institute of Biomedical Engineering and Biomaterials, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea.

Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 May;98:42-53. doi: 10.1016/j.msec.2018.12.127. Epub 2018 Dec 29.

Abstract

Herein, we report a functionalized alginate(Alg)-based terpolymeric semi-interpenetrating (semi-IPN) hydrogel, synthesized via free radical polymerization for the delivery of bovine albumin serum (BSA) and 5-amino salicylic acid (5-ASA). To improve mechanical properties, and to modulate surface morphology of Alg, 2-hydroxyethyl acrylate (HEA) was grafted on alginate and then crosslinked using poly(ethylene glycol) diacrylate (PEGDA). The probable structure and compositions of the synthesized semi-IPN terpolymer were identified by FTIR, H-HR-MAS NMR, and TGA analyses. Achievement of equilibrium swelling state (ESS) and higher elastic modulus values confirmed terpolymer gel formation in aqueous media. Differences in the ESS of the prepared gel at pH 2.5 and 7.4 signify its stimuli-responsive behaviour. The influence of PEGDA on swelling, mechanical properties, surface morphology, cell viability and proliferation, and BSA and 5-ASA delivery were characterized. SEM images show that higher % PEGDA resulted in smaller sized pores in the gel network. Texture analyses demonstrate that hardness, adhesiveness and chewiness of the gel were enhanced at higher PEGDA concentrations. Increases in PEGDA concentration also induced increases in osteoblastic cell viability and higher rates of cell proliferation compared with gels containing lower concentrations of PEGDA. The release results indicate that the gels containing higher concentrations of PEGDA more sustainably release BSA and 5-ASA at 5 days and 30 h, respectively. The experimental data revealed that the synthesized terpolymeric semi-IPN hydrogel may have useful biomedical applications, especially as a carrier of protein (BSA), or 5-ASA (a therapeutic option for conditions of the colon such as Crohn's Disease and Ulcerative Colitis).

摘要

在此,我们报告了一种基于功能化海藻酸钠(Alg)的三元半互穿(semi-IPN)水凝胶,该水凝胶通过自由基聚合合成,用于输送牛血清白蛋白(BSA)和 5-氨基水杨酸(5-ASA)。为了提高机械性能并调节 Alg 的表面形态,将 2-羟乙基丙烯酰胺(HEA)接枝到海藻酸钠上,然后使用聚乙二醇二丙烯酸酯(PEGDA)交联。通过 FTIR、H-HR-MAS NMR 和 TGA 分析鉴定了合成的半互穿三元共聚物的可能结构和组成。在水介质中达到平衡溶胀状态(ESS)和更高弹性模量值证实了三元共聚物凝胶的形成。在 pH 2.5 和 7.4 下制备凝胶的 ESS 差异表明其具有刺激响应行为。研究了 PEGDA 对溶胀、力学性能、表面形态、细胞活力和增殖以及 BSA 和 5-ASA 递送的影响。SEM 图像表明,PEGDA 的更高百分比导致凝胶网络中孔的尺寸更小。纹理分析表明,随着 PEGDA 浓度的增加,凝胶的硬度、粘性和咀嚼性得到提高。与含有较低 PEGDA 浓度的凝胶相比,PEGDA 浓度的增加也会诱导成骨细胞活力增加和细胞增殖率更高。释放结果表明,含有较高 PEGDA 浓度的凝胶在第 5 天和第 30 小时分别更可持续地释放 BSA 和 5-ASA。实验数据表明,合成的三元半互穿水凝胶可能具有有用的生物医学应用,特别是作为蛋白质(BSA)或 5-ASA(治疗结肠疾病如克罗恩病和溃疡性结肠炎的选择)的载体。

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