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Enzyme- and cell-mediated degradation of poly(ethylene carbonate) by surface erosion
Polymer Degradation and Stability ( IF 5.9 ) Pub Date : 2018-11-16 , DOI: 10.1016/j.polymdegradstab.2018.11.018
Adam Bohr , Kaveh Memarzadeh , Necati Harmankaya , Moritz Beck-Broichsitter

Poly(ethylene carbonate) (PEC) is a biodegradable polymer with attractive properties for controlled drug delivery applications. However, the mechanisms by which the polymer is degraded and the control hereof are not yet completely understood. Here, we investigated the degradation behavior of PEC films in vitro in the presence of distinct enzymes, cells, bacteria and tissue homogenates.

PEC was degraded by a surface erosion process (constant molecular weight with an almost linear mass loss during incubation). Of the enzymes tested, only cholesterol esterase from porcine pancreas and lipase from Thermomyces lanuginosus caused significant polymer erosion. Enzymatic degradation was arrested by the addition of a protease inhibitor cocktail. Furthermore, PEC films, which were exposed to the macrophage cell lines RAW 264.7 and J774.1 showed a rapid degradation profile. The polymer erosion process triggered by phagocytes was dose-dependently diminished in the presence of vitamin C. When PEC films were incubated with pancreas homogenate no measurable degradation by mass was detected. However, scanning electron microscopy analysis showed signs of erosion on the surface of the polymer samples.

Overall, this study identified specific enzymes, cells and organ homogenates, which degraded PEC in vitro and thus, should be involved in the clinical picture to facilitate an on-demand drug release at the diseased site of action. Application of enzyme inhibitors and antioxidants further highlighted the relevant role of radicals during macrophage-triggered degradation of PEC.



中文翻译:

酶和细胞介导的表面腐蚀对聚碳酸亚乙酯的降解

聚(碳酸亚乙酯)(PEC)是一种具有可生物降解的聚合物,具有吸引人的特性,可用于受控的药物输送应用。但是,聚合物降解的机理及其控制尚不完全清楚。在这里,我们研究了在存在不同酶,细胞,细菌和组织匀浆的情况下,PEC膜在体外的降解行为。

PEC通过表面腐蚀过程降解(恒定分子量,在培养过程中质量损失几乎线性)。在测试的酶中,只有来自猪胰腺的胆固醇酯酶和来自嗜热单胞菌的脂肪酶才引起明显的聚合物侵蚀。通过添加蛋白酶抑制剂混合物阻止酶降解。此外,暴露于巨噬细胞系RAW 264.7和J774.1的PEC膜表现出快速降解特性。在维生素C的存在下,吞噬细胞触发的聚合物侵蚀过程呈剂量依赖性降低。当PEC膜与胰腺匀浆一起孵育时,未检测到质量可测的降解。然而,扫描电子显微镜分析显示出聚合物样品表面上腐蚀的迹象。

总的来说,这项研究确定了在体外降解PEC的特定酶,细胞和器官匀浆,因此应参与临床研究,以促进按需释放药物在患病部位。酶抑制剂和抗氧化剂的应用进一步强调了自由基在巨噬细胞触发的PEC降解过程中的相关作用。

更新日期:2018-11-16
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