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基于聚乙二醇和聚对苯二甲酸丁二醇酯的聚(醚酯)嵌段共聚物的体内和体外降解

In vivo and in vitro degradation of poly(ether ester) block copolymers based on poly(ethylene glycol) and poly(butylene terephthalate).

作者信息

Deschamps A A, van Apeldoorn A A, Hayen H, de Bruijn J D, Karst U, Grijpma D W, Feijen J

机构信息

Department of Polymer Chemistry and Biomaterials, Faculty of Chemical Technology, Institute for Biomedical Technology (BMTI), University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.

出版信息

Biomaterials. 2004 Jan;25(2):247-58. doi: 10.1016/s0142-9612(03)00495-2.

Abstract

Two in vivo degradation studies were performed on segmented poly(ether ester)s based on polyethylene glycol (PEG) and poly(butylene terephthalate) (PBT) (PEOT/PBT). In a first series of experiments, the in vivo degradation of melt-pressed discs of different copolymer compositions were followed up for 24 weeks after subcutaneous implantation in rats. The second series of experiments aimed to simulate long-term in vivo degradation. For this, PEOT/PBT samples were pre-degraded in phosphate buffer saline (PBS) at 100 degrees C and subsequently implanted. In both series, explanted materials were characterized by intrinsic viscosity measurements, mass loss, proton nuclear magnetic resonance spectroscopy (1H-NMR) and differential scanning calorimetry (DSC). In both studies the copolymer with the higher PEO content degraded the fastest, although all materials degraded relatively slowly. To determine the nature of the degradation products formed during hydrolysis of the copolymers, 1000 PEOT71PBT29 (a copolymer based on PEG with a molecular weight of 1000 g/mol and 71 wt% of PEO-containing soft segments) was degraded in vitro at 100 degrees C in phosphate buffer saline (PBS) during 14 days. The degradation products present in PBS were analyzed by 1H-NMR and high performance liquid chromatography/mass spectroscopy (HPLC/MS). These degradation products consisted of a fraction with high contents of PEO that was soluble in PBS and a PEOT/PBT fraction that was insoluble at room temperature. From the different in vitro and in vivo degradation experiments performed, it can be concluded that PEOT/PBT degradation is a slow process and generates insoluble polymeric residues with high PBT contents.

摘要

对基于聚乙二醇(PEG)和聚对苯二甲酸丁二醇酯(PBT)的嵌段聚(醚酯)(PEOT/PBT)进行了两项体内降解研究。在第一系列实验中,将不同共聚物组成的熔融压制圆盘皮下植入大鼠体内后,对其体内降解情况进行了24周的跟踪。第二系列实验旨在模拟长期体内降解。为此,将PEOT/PBT样品在100℃的磷酸盐缓冲盐水(PBS)中进行预降解,随后植入。在这两个系列中,通过特性粘度测量、质量损失、质子核磁共振光谱(1H-NMR)和差示扫描量热法(DSC)对取出的材料进行表征。在两项研究中,尽管所有材料降解相对较慢,但聚环氧乙烷(PEO)含量较高的共聚物降解最快。为了确定共聚物水解过程中形成的降解产物的性质,将1000 PEOT71PBT29(一种基于分子量为1000 g/mol的PEG且含有71 wt%含PEO软段的共聚物)在100℃的磷酸盐缓冲盐水(PBS)中体外降解14天。通过1H-NMR和高效液相色谱/质谱联用(HPLC/MS)分析PBS中存在的降解产物。这些降解产物由两部分组成,一部分是在PBS中可溶的、PEO含量高的部分,另一部分是在室温下不溶的PEOT/PBT部分。从所进行的不同体外和体内降解实验可以得出结论,PEOT/PBT降解是一个缓慢的过程,并产生具有高PBT含量的不溶性聚合物残留物。

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