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基于聚(醚酯)嵌段共聚物的蛋白质控释系统:聚合物网络表征

A controlled release system for proteins based on poly(ether ester) block-copolymers: polymer network characterization.

作者信息

Bezemer J M, Grijpma D W, Dijkstra P J, van Blitterswijk C A, Feijen J

机构信息

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

出版信息

J Control Release. 1999 Dec 6;62(3):393-405. doi: 10.1016/s0168-3659(99)00170-4.

Abstract

The properties of a series of multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(butylene terephthalate) (PBT) blocks were investigated with respect to their application as a matrix for controlled release of proteins. The degree of swelling, Q, of the copolymers increased with increasing PEG content and with increasing molecular weight of the PEG segment. Within the composition range tested, Q varied from 1.26 for polymers with PEG segments of 600 g/mol and a PBT content of 60 weight.% up to 3.64 for polymers with PEG segments of 4000 g/mol and a PEG/PBT weight ratio of 80:20. Equilibrium stress (compression)-strain measurements were performed in order to estimate mesh sizes. The mesh size of the copolymers ranged from 38 to 93 A, which was experimentally confirmed by diffusion of vitamin B(12) (hydrodynamic diameter d(h)=16.6 A), lysozyme (d(h)=41 A) and bovine serum albumin (d(h)=72 A). The in vitro degradation of PEG/PBT copolymers with a PEG block length of 1000 g/mol and PEG/PBT weight ratios of 70:30, 60:40 and 40:60 was studied. Matrices with increasing PEG contents exhibited a faster weight loss in phosphate-buffered saline (pH 7.4) at 37 degrees C. Over a degradation period of 54 days, M(n) decreased by about 35-45%, while the composition of the matrices, determined by NMR, remained almost constant.

摘要

研究了一系列基于亲水性聚乙二醇(PEG)和疏水性聚对苯二甲酸丁二醇酯(PBT)嵌段的多嵌段共聚物作为蛋白质控释基质的性能。共聚物的溶胀度Q随PEG含量的增加以及PEG链段分子量的增加而增大。在所测试的组成范围内,对于PEG链段为600 g/mol且PBT含量为60重量%的聚合物,Q为1.26;而对于PEG链段为4000 g/mol且PEG/PBT重量比为80:20的聚合物,Q高达3.64。进行了平衡应力(压缩)-应变测量以估计网孔尺寸。共聚物的网孔尺寸范围为38至93 Å,这通过维生素B12(流体动力学直径d(h)=16.6 Å)、溶菌酶(d(h)=41 Å)和牛血清白蛋白(d(h)=72 Å)的扩散得到了实验证实。研究了PEG嵌段长度为1000 g/mol且PEG/PBT重量比为70:30、60:40和40:60的PEG/PBT共聚物的体外降解情况。PEG含量增加的基质在37℃的磷酸盐缓冲盐水(pH 7.4)中表现出更快的重量损失。在54天的降解期内,M(n)下降了约35 - 45%,而通过核磁共振测定的基质组成几乎保持不变。

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