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

被引:81
作者
Bezemer, JM
Grijpma, DW
Dijkstra, PJ
van Blitterswijk, CA
Feijen, J
机构
[1] Univ Twente, Fac Chem Engn, Inst Biomed Technol, NL-7500 AE Enschede, Netherlands
[2] Leiden Univ, Biomat Res Grp, NL-2300 RA Leiden, Netherlands
[3] IsoTis BV, NL-3723 MB Bilthoven, Netherlands
关键词
block-copolymer; protein release; mesh size; permeability; degradation;
D O I
10.1016/S0168-3659(99)00170-4
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 PET 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 Angstrom, which was experimentally confirmed by diffusion of vitamin B-12 (hydrodynamic diameter d(h) = 16.6 Angstrom), lysozyme (d(h) = 41 Angstrom) and bovine serum albumin (d(h) = 72 Angstrom). The in vitro degradation of PEG/PET copolymers with a PEG block length of 1000 g/mol and PEG/PET 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. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:393 / 405
页数:13
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