Modification of polymers for cardiovascular applications—some routes to bioactive hydrophilic polymers

Abstract

This paper is concerned with the activation of platelets by polymers, a keyprocess 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 in in 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 haloacyloisocyanates and 2-isocyanatoethyl methacrylate as reagents.

Modification of Biomaterials to Improve Blood Compatibility

“…These side-chains behave as spacers separating the bioactive units from the polymer backbonesthe spacer length is often an important feature influencing bioactivity in such systems. The spacer may be hydrophilic (CH 2CH 2 0 )n or hydrophobic (CH 2CH 2 )m' We have found significant effects on the molar activity of coupled BW 245C produced by variations in spacer length and hydrophilicity in polymers based on N-vinyl pyrrolidone (R = ot:J ) studied in aqueous solution (11,14).…”

“…We shall see later that as far as platelet adhesion is concerned, the compounds [14,15,16] confer a significant degree of passivity on polymer surfaces to which they are attached.…”

“…This represents a portion of the polymer chain; the proportions of BW 245C and vinyl monomer units are [5) [12] to the urethane linkages and used as free radical sources (with the aid of the metal carbonyl processes already outlined) (18,19) to graft on the BW 245C-monomer ( [5], n=1) and DI MA [11] and many other species. Interesting monomers [14], [15], have been prepared from several a-amino acids and also from amino sugars, e.g. glucamine, by reacting these compounds with [13].…”

Professor Bamford's research in the field of biomaterials

“…It was natural to extend the applicability of this synthetic route by converting polyethylene glycol into a macromer with terminal vinyl functionality. For this purpose reaction of polyethylene glycol and a vinyl isocyanate, such as 2-isocyanato ethyl methacrylate, was effected [9,14], as illustrated in Scheme 5.…”

Easily grafted polyurethanes with reactive main chain functional groups. Synthesis, characterization, and antithrombogenicity of poly(ethylene glycol)-grafted poly(urethanes)

“…27 Much research has been directed towards grafted poly(ether urethanes). Previous methods of incorporating PEG grafts onto a poly-(urethane) include preparation of surface physical interpenetrating networks (SPIN), 28 covalent grafting onto the urethane group through an allophanate linkage, 29 or onto main chain fumaramide double bonds of a poly(ether urethane amide) via Michael addition of an amine terminated PEG. 30 Kohn et al 31 prepared polyurethanes from bis-hydroxysuccinimidyl PEG carbonates and lysine esters, which, after hydrolysis, had pendant carboxylic acids.…”