Synthesis and characterization of polystyrene–poly(ethylene oxide)–heparin block copolymers

Abstract

SynopsisA procedure for the preparation of new block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic spacer-block of poly(ethy1ene oxide) and a bioactive block of heparin was investigated. Polystyrene with one amino group per chain was synthesized by free radical oligomerhtion of styrene in dimethylformamide, using 2-aminoethanethiol as a chain transfer agent. This amino group was used in the coupling reaction with amino-telechelic poly(ethy1ene oxide) to produce an AB type diblock copolymer with one amino group per polystyrene (PSt)-poly(ethy1ene oxide) (PEO) chain. The amino-semitelechelic oligestyrene was converted into the isocyanatrsemitelechelic oligo-styrene using toluene 2,4diisocyanate and subsequent coupling with H,N-PEO-NH, afforded AB type block copolymers with terminal amino groups.The coupling of PSt-PEO-NH, with heparin was performed in a DMF-H,O mixture, first by activating the heparin carboxylic groups with EDC at pH 5.1-52 and subaequently reading the activated carboxylic groups with the amino groups of the PSt-PEO-NH2 at pH 7.5. Depending on the molecular weights of the diblock copolymer used 25-29% w/w heparin was incorporated. Thew polymers will be further evaluated for their blood-compatibility.

Evaluation of biocompatibility of the surface of polyethylene films modified with various water soluble polymers using Ar plasma-post polymerization technique

“…[6][7][8][9] In particular, since a hydrogel has physical properties similar to human tissue and may exhibit an excellent biocompatibility, a number of workers have made a significant effort to modify the surface of polymer substrates with hydrogel forming polymers such as poly [2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC), [1,[10][11] poly [2-(glucosyloxy)ethyl methacrylate] (PGEMA), [2,3] polyoxyethylene (POE), [12] poly(N-isopropylacrylamide) (PNIPAAm) [13] and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA), [14,15] the structures are shown in Fig. 1.…”

Heparin-containing block copolymers

“…Aminotelechelic poly(ethylen e oxide), with a molecular weight of 4000 (H2N-PEO(4000)-NH2), was a generous gift from Nippon Oil and Fats Company Ltd, Ibaraki, Japan and was characterized as described previously [13].…”

“…Polystyrene-poly(ethylene oxide)-heparin (PS-PEO-Hep) block copolymers were synthesized by: (a) coupling of PS-PEO-NH2 with heparin performed in a DMF-H20 (40:1 v/v) mixture, first by activating carboxylic acid groups of heparin with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and subsequently reacting the activated carboxylic acid groups with amino groups of PS-PEO-NH2, as described before [13]; and (b) coupling of PS-PEO-NHz with nitrous acid-degraded heparin performed in a DMF-H20 (40: i vjv) mixture, using cyanoborohydride as reducing agent, also described previously [14,15]. An overview of the prepared block copolymers is shown in Table I.…”

“…Polystyrene-poly(ethylene oxide) (PS-PEO) diblock copolymers were synthesized by a coupling reaction of aminosemitelechelic polystyrene with aminotelechelic poly(ethylene oxide), using toluene 2,4-diisocyanate as coupling agent, according to the procedures described previously [13][14][15].…”

Professor Jan Feijen: A pioneer in biomedical polymers and controlled drug release

“…In addition to synthetic polymers, he has also carried out extensive work on chemical modifications of natural polymers for various biomedical uses. For example, he has prepared various copolymers of heparins such as polystyrene-poly(ethylene oxide)-heparin [28] and poly(dimethylsiloxane)-poly(ethylene oxide)-heparin block copolymers [29], and albumin-heparin conjugates [30,31] which were used to improve the blood compatibility of polymeric biomaterials. He has developed different approaches e.g.…”