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氧化还原可还原且可水解降解的聚乙二醇-聚乳酸弹性体作为临时药物洗脱医疗器械的生物材料

Redox Reducible and Hydrolytically Degradable PEG-PLA Elastomers as Biomaterial for Temporary Drug-Eluting Medical Devices.

作者信息

Rupnik Simona, Buwalda Sytze, Dejean Stéphane, Bethry Audrey, Garric Xavier, Coudane Jean, Nottelet Benjamin

机构信息

Institute of Biomolecules Max Mousseron (IBMM) UMR 5247, Department of Artificial Biopolymers, CNRS, University of Montpellier, ENSCM. Faculté de Pharmacie 15 avenue Charles Flahault BP14491, 34093, Montpellier CEDEX 5, France.

出版信息

Macromol Biosci. 2016 Dec;16(12):1792-1802. doi: 10.1002/mabi.201600132. Epub 2016 Jul 5.

Abstract

With the aim to develop biomaterials for temporary medical devices, a series of novel reducible and/or degradable elastomers has been prepared from PLA-b-PEG-b-PLA copolymers photo-crosslinked with diallyl sulfide or pentaerythritol tetrakis(3-mercaptopropionate). Thermal and mechanical properties, including elastic limit and Young modulus, are assessed. Degradation is then evaluated under standard hydrolytic conditions. Reducibility of a selected elastomer is then illustrated using 2-mercaptoethanol or glutathione as reducing agents. The redox-sensitivity of the selected elastomer and the possibility to modulate the degradability are shown. Considering drug-eluting elastomeric devices applications, anti-inflammatory drug ibuprofen loading is illustrated with the two simplest elastomer formulations. A rapid or slow linear release is observed as a function of the low or high molecular weight of the triblock pre-polymers. Finally, the cytocompatibility of the degradable elastomers is assessed with regard to their potential to favor or inhibit L929 murine fibroblasts proliferation as a function of the hydrophilicity/hydrophobicity of the triblock copolymers.

摘要

为了开发用于临时医疗设备的生物材料,通过用二烯丙基硫醚或季戊四醇四(3-巯基丙酸酯)对聚乳酸- b -聚乙二醇- b -聚乳酸共聚物进行光交联,制备了一系列新型的可还原和/或可降解弹性体。评估了包括弹性极限和杨氏模量在内的热性能和机械性能。然后在标准水解条件下评估降解情况。接着用2-巯基乙醇或谷胱甘肽作为还原剂来说明所选弹性体的可还原性。展示了所选弹性体的氧化还原敏感性以及调节降解性的可能性。考虑到药物洗脱弹性体装置的应用,用两种最简单的弹性体配方说明了抗炎药物布洛芬的负载情况。观察到快速或缓慢的线性释放是三嵌段预聚物低分子量或高分子量的函数。最后,根据三嵌段共聚物的亲水性/疏水性,评估了可降解弹性体对L929小鼠成纤维细胞增殖的促进或抑制潜力,以此评估其细胞相容性。

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