Tunable hydrogel for encapsulation and controlled release of bioactive proteins

Tunable hydrogel for encapsulation and controlled release of bioactive proteins
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DOI:
10.1021/bm010147y
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发表时间:
2002-03-01
期刊:
影响因子:
6.2
通讯作者:
Janda, KD
Janda, KD
中科院分区:
化学2区
文献类型:
--
作者:
Delgado, M;Spanka, C;Janda, KD

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以新型交联剂(乙二氧基)双[2,2‘-(N-丙烯酰氨基)乙烷](1)为交联剂,制备了N,N-二甲基丙烯酰胺水凝胶(2),并研究了其在水溶液中的物理化学性质。将三种不同的天然蛋白(溶菌酶、牛血清白蛋白和兔免疫球蛋白)包裹在聚合物基质2中,并测定了它们从溶胀水凝胶中释放的动力学。蛋白质的释放速率明显依赖于蛋白质的相对分子质量和用于制备水凝胶的交联剂的量。这反映在低分子量蛋白质比高分子量蛋白质释放的速度更快的事实上。此外,交联剂的比例越低,水凝胶释放出的蛋白质越多。本研究中使用的聚合过程足够温和,可以确保伴随的生物分子的功能完整性,这是通过保持包裹的a-胰凝乳蛋白酶和醛缩酶催化抗体38C2的催化活性来确定的。由于这些水凝胶对人皮肤成纤维细胞无毒性,在小鼠体内缺乏免疫原性,因此它们在体内控制释放生物活性物质的潜在用途得到了加强。
A N,N-dimethylacrylamide-based hydrogel (2) with the new cross-linker (ethylenedioxy) bis[2,2'-(N-acryloylamino)ethane] (1) has been prepared, and its physicochemical properties in aqueous solution were studied. Three different native proteins (lysozyme, bovine serum albumin, and rabbit IgG) were encapsulated within the polymeric matrix 2, and the kinetics of their release from the swollen hydrogel were determined. The rate of protein release exhibits a clear dependence on both the molecular weight of the protein and the amount of cross-linker utilized to prepare the hydrogel. This is reflected by the fact that the low molecular weight proteins are released at an increased rate versus higher molecular weight proteins. In addition a greater amount of protein is released from the hydrogels with a lower percentage of cross-linker. The polymerization procedure used in this study is sufficiently mild to safeguard the functional integrity of attendant biomolecules as determined by the retention of catalytic activity of encapsulated a-chymotrypsin and aldolase catalytic antibody 38C2. The potential utility of these hydrogels for the controlled release of bioactive agents in vivo is strengthened by both their lack of toxicity against human dermal fibroblasts and their lack of immunogenicity in mice.