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具有增强的蛋白质负载和释放效率的微结构智能水凝胶。

Micro-structured smart hydrogels with enhanced protein loading and release efficiency.

机构信息

Institute of Materials Science and Technology (IMT), Chair in Materials Science, Friedrich-Schiller-University Jena, Löbdergraben 32, D-07743 Jena, Germany.

出版信息

Acta Biomater. 2010 Apr;6(4):1297-306. doi: 10.1016/j.actbio.2009.11.005. Epub 2009 Nov 12.

DOI:10.1016/j.actbio.2009.11.005
PMID:19913647
Abstract

A series of temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with highly porous microstructures were successfully prepared by using hydrophobic polydimethylsiloxane (PDMS) and sodium dodecyl sulfate as liquid template and stabilizer, respectively. These newly prepared hydrogels possess highly porous structures. In contrast to the conventional PNIPAAm hydrogel, the swelling ratios of the porous gels at room temperature were higher, and their response rates were significantly faster as the temperature was raised above the lower critical solution temperature. For example, the novel hydrogel prepared with 40% PDMS template lost over 95% water within 5 min, while the conventional PNIPAAm gel only lost approximately 14% water in the same time. The improved properties are achieved due to the presence of liquid PDMS templates in the reaction solutions, which lead to the formation of porous structures during the polymerization/crosslinking. Lysozyme and bovine serum albumin (BSA) as protein models were for the first time loaded into these micro-structured smart hydrogels through a physical absorption method. The experimental results show that the loading efficiency of BSA with a higher molecular weight is lower than that of lysozyme due to the size exclusion effect, and the loading efficiencies of both proteins in the porous hydrogel are much higher than those in the conventional PNIPAAm hydrogel. For example, the loading efficiency of BSA in porous hydrogel is 0.114, approximately 200% higher than that in conventional hydrogel (0.035). Both lysozyme and BSA were completely released from the porous hydrogel at 22 degrees C. Furthermore, the release kinetics of the proteins from the porous hydrogel could be modulated by tuning the environmental temperature. These newly prepared porous materials provide an avenue to increase the loading efficiency and to control the release patterns of macromolecular drugs from hydrogels, and show great promise for application in protein or gene delivery.

摘要

一系列具有高度多孔微观结构的温度响应性聚(N-异丙基丙烯酰胺)(PNIPAAm)水凝胶通过使用疏水性聚二甲基硅氧烷(PDMS)和十二烷基硫酸钠分别作为液体模板和稳定剂成功制备。这些新制备的水凝胶具有高度多孔的结构。与传统的 PNIPAAm 水凝胶相比,多孔凝胶在室温下的溶胀率更高,当温度升高到低于临界溶液温度以上时,其响应速度明显更快。例如,用 40%PDMS 模板制备的新型水凝胶在 5 分钟内失去超过 95%的水,而在相同时间内,传统的 PNIPAAm 凝胶仅失去约 14%的水。由于反应溶液中存在液体 PDMS 模板,导致聚合/交联过程中形成多孔结构,从而实现了性能的提高。溶菌酶和牛血清白蛋白(BSA)作为蛋白质模型首次通过物理吸收方法被负载到这些微结构智能水凝胶中。实验结果表明,由于尺寸排阻效应,具有较高分子量的 BSA 的负载效率低于溶菌酶,并且多孔水凝胶中两种蛋白质的负载效率都远高于传统的 PNIPAAm 水凝胶。例如,BSA 在多孔水凝胶中的负载效率为 0.114,约比传统水凝胶(0.035)高 200%。溶菌酶和 BSA 均在 22°C 时完全从多孔水凝胶中释放。此外,通过调节环境温度可以调节蛋白质从多孔水凝胶中的释放动力学。这些新制备的多孔材料为提高水凝胶中大分子药物的负载效率和控制其释放模式提供了一种途径,并有望在蛋白质或基因传递中得到应用。

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