Modification of polymers for cardiovascular applications—some routes to bioactive hydrophilic polymers
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This paper is concerned with the activation of platelets by polymers, a key-process in the behaviour of prosthetic devices in contact with blood.
Platelets are activated by contact with many different types of polymer surfaces, which must therefore be regarded as thrombogenic. Two procedures for reducing thrombogenicity are discussed: (i) the chemical attachment of inhibitors of platelet aggregation and (ii) gross modification of the nature of the surface, e.g. by making it more hydrophilic. For purposes of (i) the potent prostaglandin analogue BW 245C has been used, while for (ii) grafting of poly(ethylene glycol) (PEG) has been explored. Both methods give greatly reduced platelet adhesion inin vitro tests.
The second part of the paper deals with the properties of adducts of inhibitors of platelet aggregation (BW 245C, dipyridamole) with water-soluble macromolecules [poly(N-vinyl pyrrolidone), PEG, dextran]. Adducts have been synthesized with terminal and side-chain coupling. On adduction the two inhibitors mentioned show opposite types of behaviour: the molar activity of BW 245C is dramatically reduced, but that of dipyridamole is significantly increased. Remarkable synergistic effects have been recorded for BW 245C adducts. These observations are interpreted in terms of differences in stereochemistry in the drug-receptor interactions.
Appropriate chemical techniques for coupling are outlined, attention being drawn to the special uses of haloalkyl- and haloacyl-isocyanates and 2-isocyanatoethyl methacrylate as reagents.
KeywordsPlatelet adhesion and aggregation prostaglandin analogue BW 245C dipyridamole poly(ether urethane urea) polystyrene poly(N-vinyl pyrrolidone) poly (ethylene glycol) dextran non-thrombogenic surface
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