一种合成的、具有 UCST 行为的瞬态热响应均聚物,其窗口在生理相关范围内。

A Synthetic, Transiently Thermoresponsive Homopolymer with UCST Behaviour within a Physiologically Relevant Window.

机构信息

Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong Province, 250012, China.

出版信息

Angew Chem Int Ed Engl. 2019 Jun 3;58(23):7866-7872. doi: 10.1002/anie.201900224. Epub 2019 Apr 30.

Abstract

Interactive materials that can respond to a trigger by changing their morphology, but that can also gradually degrade into a fully soluble state, are attractive building blocks for the next generation of biomaterials. Herein, we design such transiently responsive polymers that exhibit UCST behaviour while gradually losing this property in response to a hydrolysis reaction in the polymer side chains. The polymers operate within a physiologically relevant window in terms of temperature, pH, and ionic strength. Whereas such behaviour has been reported earlier for LCST systems, it is at present unexplored for UCST polymers. Furthermore, we demonstrate that, in contrast to LCST polymers, in aqueous medium the UCST polymer forms a coacervate phase below the UCST, which can entrap a hydrophilic model protein, as well as a hydrophobic dye. Because of their non-toxicity, we also provide in vivo proof of concept of the use of this coacervate as a protein depot, in view of sustained-release applications.

摘要

能够通过改变形态来响应触发因素,但也可以逐渐降解为完全可溶性状态的交互式材料,是下一代生物材料的有吸引力的构建块。在此,我们设计了这种瞬态响应聚合物,它们在表现出 UCST 行为的同时,会逐渐失去这种特性,以响应聚合物侧链上的水解反应。这些聚合物在温度、pH 值和离子强度方面都在生理相关的窗口内运行。虽然这种行为在 LCST 系统中已经有报道,但目前还没有针对 UCST 聚合物的研究。此外,我们还证明,与 LCST 聚合物相反,在水性介质中,UCST 聚合物在 UCST 以下形成凝聚相,该凝聚相可以包裹亲水性模型蛋白和疏水性染料。由于其毒性低,我们还提供了体内实验证明,这种凝聚相可用作蛋白质库,以实现持续释放应用。

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