Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels
Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels
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DOI：
10.1016/j.jconrel.2007.06.011
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发表时间：
2007-09-11
影响因子：
10.8
通讯作者：
Feijen, Jan
中科院分区：
文献类型：
--
作者：
Hiemstra, Christine;Zhong, Zhiyuan;Feijen, Jan
我们之前的研究表明，通过Michael加成将葡聚糖乙烯砜（dex-VS）偶联物和四功能巯基聚乙二醇（PEG-4-SH）水溶液混合，可在原位快速形成可降解的葡聚糖水凝胶。水凝胶的降解时间和储存模量可由乙烯砜取代度和葡聚糖分子量控制。降解时间可以进一步通过在dex-VS偶联物的硫醚和酯键之间的间隔来调节（乙基对丙基，分别记为dex-Et-VS和dex-Pr-VS）。本文研究了原位形成的葡聚糖水凝胶对免疫球蛋白G （d(h)=10.7 nm, IgG）、牛血清白蛋白（d(h)= 7.2 nm）和溶菌酶（d(h)=4.1 nm）三种模型蛋白以及碱性成纤维细胞生长因子（bFGF）的释放。通过混合含有dex-VS和PEG-4-SH的蛋白质溶液，可以很容易地将蛋白质装载到水凝胶中。dex-Et-VS水凝胶中IgG的释放遵循双相释放动力学，前9天缓慢释放，接近一阶释放，随后加速释放，12 ~ 25天内IgG释放量超过80%。有趣的是，从dex-Pr-VS水凝胶中释放IgG遵循接近零级动力学，其中约95%在21天内释放。dex-Pr-VS水凝胶中BSA的释放遵循双相动力学，几乎是一级释放，然后是接近零级释放。大约75%的BSA可以在16天内从dex-Pr-VS水凝胶中释放出来。根据细菌裂解实验，Dex-Pr-VS水凝胶在14天内释放40%的溶菌酶，并充分保存了释放的溶菌酶的酶活性。碱性成纤维细胞生长因子（bFGF）从dex-Pr-VS水凝胶中释放为一级动力学，在28天内定量释放。这些结果表明，原位形成的可降解葡聚糖水凝胶可以用于蛋白质的控制释放。(c) 2007 Elsevier B.V.版权所有
Our previous studies showed that degradable dextran hydrogels are rapidly formed in situ upon mixing aqueous solutions of dextran vinyl sulfone (dex-VS) conjugates and tetrafunctional mercapto poly(ethylene glycol) (PEG-4-SH) by Michael addition. The hydrogel degradation time and storage modulus could be controlled by the degree of vinyl sulfone substitution (DS) and dextran molecular weight. The degradation time could further be adjusted by the spacer between the thioether and the ester bond of the dex-VS conjugates (ethyl vs. propyl, denoted as dex-Et-VS and dex-Pr-VS, respectively). In this paper, the release of three model proteins, i.e. immunoglobulin G (d(h)=10.7 nm, IgG), bovine serum albumin (BSA, d(h)=7.2 nm) and lysozyme (d(h)=4.1 nm), as well as basic fibroblast growth factor (bFGF) from these in situ forming dextran hydrogels is studied. Proteins could be easily loaded into the hydrogels by mixing protein containing solutions of dex-VS and PEG-4-SH. The release of IgG from dex-Et-VS hydrogels followed biphasic release kinetics, with a slow, close to first order release for the first 9 days followed by an accelerated release and over 80%, of IgG was released in 12 to 25 days. Interestingly, the release of IgG from dex-Pr-VS hydrogels followed close to zero order kinetics, wherein approximately 95% was released in 21 days. The release of BSA from dex-Pr-VS hydrogels followed biphasic kinetics, with almost first order release followed by close to zero order release. Approximately 75% of the entrapped BSA could be released from dex-Pr-VS hydrogels in 16 days. Dex-Pr-VS hydrogels released 40% of lysozyme in 14 days, with full preservation of the enzymatic activity of the released lysozyme, as determined by bacteria lysis experiments. The release of basic fibroblast growth factor (bFGF) from dex-Pr-VS hydrogels showed first order kinetics, with quantitative release in 28 days. These results show that the in situ forming degradable dextran hydrogels can be used for the controlled release of proteins. (c) 2007 Elsevier B.V. All rights reserved.