Enhanced protein delivery from photopolymerized hydrogels using a pseudospecific metal chelating ligand
Enhanced protein delivery from photopolymerized hydrogels using a pseudospecific metal chelating ligand
复制标题
DOI：
10.1007/s11095-005-9395-x
复制
发表时间：
2006-03-01
影响因子：
3.7
通讯作者：
Metters, AT
中科院分区：
文献类型：
--
作者：
Lin, CC;Metters, AT
目的。本研究旨在探讨聚乙二醇光聚合水凝胶中蛋白质释放不完全的原因，并验证亚氨基二乙酸(IDA)对蛋白质的保护机制。研究了不同条件下制备的聚乙二醇水凝胶对牛血清白蛋白(BSA)的体外释放行为。光引发剂和初始蛋白浓度不同，IDA和金属离子的加入也不同。凝胶电泳法证实蛋白质通过自由基反应固定在不可降解的网络中。蛋白质的释放效率依赖于光引发剂和初始蛋白质浓度。凝胶电泳结果显示蛋白质被固定在聚合物网络上，进一步表明自由基在降低蛋白质释放效率中的不利作用。将IDA添加到预聚体溶液中，以剂量依赖的方式增加了随后光聚合网络的总蛋白释放。金属离子的添加包括Cu2+、Zn2+。Ni2+进一步提高了BSA的释放效率。蛋白质释放数据与可逆蛋白质-IDA结合的理论模型预测的一致性进一步验证了IDA和IDA-过渡金属络合物提供的保护作用。这项研究中描述的保护作用为提高许多具有治疗价值的蛋白质的传递效率提供了一种新的策略。
Purpose. This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA).Methods. The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared under different conditions was Studied. Photoinitiator and initial protein concentrations were varied as well as the addition of IDA and metal ions. Protein immobilization within the nondegradable networks via free-radical reaction was demonstrated by gel electrophoresis.Results. Protein release efficiency was shown to be dependent on photoinitiator and initial protein concentration. Gel electrophoresis results revealed immobilization of protein to the polymer network and further indicated the detrimental role of free radicals in lowering protein-release efficiency. Adding IDA to the prepolymer solution enhanced total protein release from the subsequently photopolymerized network in a dose-dependent manner. The addition of metal ions including Cu2+, Zn2+. and Ni2+ further increased BSA release efficiency. Agreement between the protein release data and theoretical model predictions accounting for reversible protein-IDA binding further validated the protection effect provided by IDA and IDA-transition metal complexes.Conclusions. The protection effect described in this study offers a novel strategy for increasing the delivery efficiencies of many therapeutically valuable proteins.