Two-layered injectable self-assembling peptide scaffold hydrogels for long-term sustained release of human antibodies
Two-layered injectable self-assembling peptide scaffold hydrogels for long-term sustained release of human antibodies
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DOI：
10.1016/j.jconrel.2012.03.014
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发表时间：
2012-06-28
影响因子：
10.8
通讯作者：
Zhang, Shuguang
中科院分区：
文献类型：
--
作者：
Koutsopoulos, Sotirios;Zhang, Shuguang
用3个月的时间研究了Ac-(RADA)(4)-CONH2和Ac-(KLDL)(3)-ConH2自组装多肽组成的纳米纤维支架水凝胶对人免疫球蛋白(IgG)的释放动力学。自组装肽是一类刺激响应性材料，在生物体液和盐类等电解质溶液存在的情况下发生溶胶-凝胶转变。随着水凝胶纳米纤维密度的增加，免疫球蛋白的扩散系数降低，为控制释放动力学提供了手段。以Ac-(RADA)(4)-CONH_2为核心，Ac-(KLDL)(3)-CONH_2为壳，形成两层水凝胶结构，通过洋葱状结构确定抗体的扩散分布。二级和三级结构分析以及单分子分析和石英晶体微天平生物测定表明，即使在水凝胶中放置3个月，包埋和释放也不影响抗体的构象和生物活性。测定了多克隆人免疫球蛋白对磷胆碱抗原的功能，结果表明，免疫球蛋白的包裹和释放不影响抗体与磷胆碱抗原的结合效果。我们的实验方案允许在水凝胶中100%的抗体负载率，而抗体的最大负载量仅取决于抗体在水中的溶解度，因为多肽水凝胶由高达99.5%的水组成。我们的结果表明，这种完全生物相容和可注射的多肽水凝胶系统可以作为治疗性抗体的载体用于控释应用。(C)2012爱思唯尔B.V.保留所有权利。
The release kinetics for human immunoglobulin (IgG) through the permeable structure of nanofiber scaffold hydrogels consisting of the ac-(RADA)(4)-CONH2 and ac-(KLDL)(3)-CONH2 self-assembling peptides were studied during a period of 3 months. Self assembling peptides are a class of stimuli-responsive materials which undergo sol-gel transition in the presence of an electrolyte solution such as biological fluids and salts. IgG diffusivities decreased with increasing hydrogel nanofiber density providing a means to control the release kinetics. Two-layered hydrogel structures were created consisting of concentric spheres of ac-(RADA)(4)-CONH2 core and ac-(KLDL)(3)-CONH2 shell and the antibody diffusion profile was determined through the 'onion-like' architecture. Secondary and tertiary structure analyses as well as biological assays using single molecule analyses and quartz crystal microbalance of the released IgG showed that encapsulation and release did not affect the conformation of the antibody and the biological activity even after 3 months inside the hydrogel. The functionality of polyclonal human IgG to the phosphocholine antigen was determined and showed that IgG encapsulation and release did not affect the antibody binding efficacy to the antigen. Our experimental protocol allows for 100% IgG loading efficiency inside the hydrogel while the maximum amount of antibody loading depends solely on the solubility of the antibody in water because the peptide hydrogel consists of water up to 99.5%. Our results show that this fully biocompatible and injectable peptide hydrogel system may be used for controlled release applications as a carrier for therapeutic antibodies. (C) 2012 Elsevier B.V. All rights reserved.