Design, synthesis, and degradation studies of new enzymatically erodible poly(hydroxyethyl methacrylate)/poly(ethylene oxide) hydrogels

Design, synthesis, and degradation studies of new enzymatically erodible poly(hydroxyethyl methacrylate)/poly(ethylene oxide) hydrogels
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DOI:
10.1116/1.2799034
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发表时间:
2007-12-01
期刊:
影响因子:
2.1
通讯作者:
Mesini, Philippe J.
Mesini, Philippe J.
中科院分区:
工程技术4区
文献类型:
--
作者:
Khelfallah, Nawel S.;Decher, Gero;Mesini, Philippe J.

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本工作描述了聚(甲基丙烯酸羟乙酯)PHEMA水凝胶的合成和研究,交联的聚(环氧乙烷)(PEO)链含有Gly-Gly- Leu三肽。选择该序列是因为其被枯草杆菌蛋白酶(一种细菌蛋白酶)切割的能力。通过将肽与两个M(w)= 3400 g/mol的氨基封端的PEO链偶联来合成交联剂。所得到的聚合物的特征在于尺寸排阻色谱,核磁共振,质谱,并被证明是很容易被切割的枯草杆菌蛋白酶。它的羟基端基酯化成甲基丙烯酸酯提供了一种大分子单体,该大分子单体用作可降解的交联剂,并与甲基丙烯酸羟乙酯共聚形成水凝胶。当PEO交联剂/聚HEMA比例增加时,凝胶的溶胀比增加。这些凝胶与酶的孵育导致凝胶的完全降解。这些试验表明,这些凝胶可用作药物递送系统,其中释放是由蛋白酶的存在引发的。(c)2007年美国真空学会。
This work describes the synthesis and the study of poly (hydroxyethyl methacrylate) PHEMA hydrogels, cross-linked by poly (ethylene oxide) (PEO) chains containing the Gly- Gly- Leu tripeptide. This sequence was selected for its ability to be cleaved by subtilisin, a bacterial protease. The cross-linker was synthesized by coupling the peptide with two amino-terminated PEO chains of M(w)= 3400 g/mol. The resulting polymer was characterized by size exclusion chromatography, nuclear magnetic resonance, and mass spectroscopy, and was shown to be readily cleaved by subtilisin. Its esterification of the hydroxyl end groups into methacrylate afforded a macromonomer that was used as a degradable cross-linker and copolymerized with hydroxyethylmethacrylate to form hydrogels. The swelling ratio of the gels increases when the PEO cross-linker/polyHEMA ratio increases. Incubation of these gels with the enzyme led to the total degradation of the gels. These assays show that these gels can be used as drug-delivery systems where the release is triggered by the presence of proteases. (c) 2007 American Vacuum Society.