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Synthetic Polymer with a Structure-Driven Hepatic Deposition and Curative Pharmacological Activity in Hepatic Cells
ACS Macro Letters ( IF 5.1 ) Pub Date : 2017-08-15 00:00:00 , DOI: 10.1021/acsmacrolett.7b00471
Camilla Frich Riber 1 , Anna Halling Folkmar Andersen 1, 2, 3 , Lærke Anegaard Rolskov 1 , Kaja Zuwala 1, 2, 3 , Paulina Gajda 1, 2, 3 , Kaja Borup Løvschall 1 , Frederik Dagnæs-Hansen 4 , Dominic H Banda 5 , Thomas Pietschmann 5 , Martin Tolstrup 2, 3 , Alexander N Zelikin 1
Affiliation  

Synthetic polymers make strong contributions as tools for delivery of biological drugs and chemotherapeutics. The most praised characteristic of polymers in these applications is complete lack of pharmacological function such as to minimize the side effects within the human body. In contrast, synthetic polymers with curative pharmacological activity are truly rare. Moreover, such activity is typically nonspecific rather than structure-defined. In this work, we present the discovery of poly(ethylacrylic acid) (PEAA) as a polymer with a suit of structure-defined, unexpected, pharmacological, and pharmacokinetic properties not observed in close structural analogues. Specifically, PEAA reveals capacity to bind to albumin with ensuing natural hepatic deposition in vivo and exhibits concurrent inhibitory activity against the hepatitis C virus and inflammation in hepatic cells. Our findings provide a view on synthetic polymers as curative, functional agents and present PEAA as a unique biomedical tool with applications related to health of the human liver.

中文翻译:

具有结构驱动肝沉积和肝细胞治疗药理活性的合成聚合物

合成聚合物作为递送生物药物和化疗药物的工具做出了巨大贡献。在这些应用中,聚合物最受赞誉的特性是完全缺乏药理功能,例如最大限度地减少人体内的副作用。相比之下,具有治疗药理活性的合成聚合物确实很少见。此外,这种活动通常是非特异性的,而不是结构定义的。在这项工作中,我们展示了聚(乙基丙烯酸)(PEAA)作为一种聚合物的发现,它具有一系列结构定义的、意想不到的、药理学和药代动力学特性,而这些特性在紧密的结构类似物中没有观察到。具体来说,PEAA 揭示了与白蛋白结合并随后在体内自然肝沉积的能力,并表现出对丙型肝炎病毒和肝细胞炎症的同时抑制活性。我们的研究结果提供了关于合成聚合物作为治疗剂、功能剂的观点,并将 PEAA 作为一种独特的生物医学工具,应用于与人类肝脏健康相关的应用。
更新日期:2017-08-15
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