Albumin hydrogels formed by electrostatically triggered self-assembly and their drug delivery capability.
Albumin hydrogels formed by electrostatically triggered self-assembly and their drug delivery capability.
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DOI：
10.1021/bm500883h
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发表时间：
2014-10-13
影响因子：
6.2
通讯作者：
Ameer, Guillermo A.
中科院分区：
文献类型：
--
作者：
Baler, Kevin;Michael, Raman;Szleifer, Igal;Ameer, Guillermo A.
生物水凝胶基本上是生物相容的，并且在医学应用和药物递送系统中与细胞外基质具有内在的相似性。在本文中，我们证明了使用一种新的机制形成药物洗脱蛋白质水凝胶的能力，该机制涉及通过改变pH值来静电触发蛋白质的部分变性和自组装。部分变性增加了蛋白质的溶剂暴露的疏水表面积，然后在37 °C下在10分钟内驱动蛋白质自组装成水凝胶。我们描述了通过这种机制形成的白蛋白水凝胶的性质。通过荧光猝灭证实，白蛋白与全反式维甲酸（atRA）的内在药物结合特性在部分变性过程中是保守的。从水凝胶释放的atRA抑制平滑肌细胞迁移，如体外划痕试验。原子分子动力学和平均力势计算表明，结合能为−41 kJ/mol的新atRA结合位点的保留和潜在创造。所得水凝胶也是生物相容的，并且在其植入体内后表现出快速的凝胶化后降解。这项跨学科的工作为生物相容性蛋白质水凝胶药物递送系统的开发提供了新的工具。
Biological hydrogels are fundamentally biocompatible and have intrinsic similarities to extracellular matrices in medical applications and drug delivery systems. Herein we demonstrate the ability to form drug-eluting protein hydrogels using a novel mechanism that involves the electrostatically triggered partial denaturation and self-assembly of the protein via changes in pH. Partial denaturation increases the protein’s solvent exposed hydrophobic surface area, which then drives self-assembly of the protein into a hydrogel within 10 min at 37 °C. We describe the properties of an albumin hydrogel formed by this mechanism. Intrinsic drug binding properties of albumin to all-trans retinoic acid (atRA) are conserved through the partial denaturation process, as confirmed by fluorescence quenching. atRA released from the hydrogel inhibited smooth muscle cell migration as per an in vitro scratch wound assay. Atomistic molecular dynamics and potential of mean force calculations show the preservation and potential creation of new atRA binding sites with a binding energy of −41 kJ/mol. The resulting hydrogel is also biocompatible and exhibits rapid postgelation degradation after its implantation in vivo. This interdisciplinary work provides a new tool for the development of biocompatible protein hydrogel drug delivery systems.
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