The effect of protein structure on their controlled release from an injectable peptide hydrogel.

The effect of protein structure on their controlled release from an injectable peptide hydrogel.
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DOI:
10.1016/j.biomaterials.2010.08.047
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发表时间:
2010-12
期刊:
影响因子:
14
通讯作者:
Schneider, Joel P.
Schneider, Joel P.
中科院分区:
工程技术1区
文献类型:
--
作者:
Branco, Monica C.;Pochan, Darrin J.;Wagner, Norman J.;Schneider, Joel P.

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水凝胶材料是一种很有前途的蛋白质治疗递送载体。蛋白质可以赋予物理相互作用,包括空间和静电性质,影响他们从给定的凝胶网络释放。在这里,不同水动力直径和电荷的模型蛋白被直接包封,并从自组装肽MAX8制备的电正性纤维水凝胶中研究它们的释放。MAX8的水凝胶化可以在蛋白质存在的情况下触发,因为它们被直接封装,不影响蛋白质结构和水凝胶的机械性能。在注射器给药前后一个月的时间内,在37°C下评估水凝胶中包裹蛋白的整体释放,以确定蛋白结构对释放的影响。带正电荷和中性蛋白的释放在很大程度上受网络施加的立体结构的支配。相反,带负电荷的蛋白质与带正电荷的纤维网络相互作用强烈,极大地限制了它们的释放,使其小于初始蛋白质负荷的10%。分配和保留研究表明,静电相互作用决定了可用于释放的蛋白质的数量。重要的是,当蛋白包膜凝胶通过注射器输送时,大分子的释放曲线显示出与未剪切凝胶相似的趋势。这项研究表明,蛋白质可以直接封装在自组装的MAX8水凝胶中,然后可以通过注射器将其输送到蛋白质结构控制的部位。
Hydrogel materials are promising vehicles for the delivery of protein therapeutics. Proteins can impart physical interactions, both steric and electrostatic in nature, that influence their release from a given gel network. Here, model proteins of varying hydrodynamic diameter and charge are directly encapsulated and their release studied from electropositive fibrillar hydrogels prepared from the self assembling peptide, MAX8. Hydrogelation of MAX8 can be triggered in the presence of proteins for their direct encapsulation with no effect on protein structure nor the hydrogel's mechanical properties. Bulk release of the encapsulated proteins from the hydrogels was assessed for a month time period at 37°C before and after syringe delivery of the loaded gels to determine the influence of protein structure on release. Release of positively charged and neutral proteins was largely governed by the sterics imposed by the network. Conversely, negatively charged proteins interacted strongly with the positively charged fibrillar network, greatly restricting their release to <10% of the initial protein load. Partition and retention studies indicated that electrostatic interactions dictate the amount of protein available for release. Importantly, when protein encapsulated gels were delivered via syringe, the release profiles of the macromolecules showed similar trends as those observed for non-sheared gels. This study demonstrates that proteins can be directly encapsulated in self assembled MAX8 hydrogels, which can then be syringe delivered to a site where subsequent release is controlled by protein structure.
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