Modification of fibrinogen with poly(ethylene glycol) and its effects on fibrin clot characteristics

The suitability of existing topical fibrin glue preparations for tissue sea ling or local drug delivery applications is greatly limited by their poor m echanical properties and the limited capacity of fibrinogen (Fgn) to active ly bind growth factors or other therapeutic agents. Poly(ethylene glycol) ( PEG) offers potential solutions to these problems by providing a mechanism for increasing the number of crosslinks between adjacent fibrin monomer mol ecules or for covalently crosslinking Fgn to therapeutic agents. The feasib ility of this approach requires the full biological activity, or clottabili ty, of PE glycolated Fgn. This study characterizes the clot characteristics of Fgn modified to varying degrees with monofunctional succinimidyl propio nate PEG (5000 Da). The data indicate that, although thrombin clotting time s are significantly altered, Fgn maintains 90% of its capacity to clot upon the addition of up to 5 PEG/Fgn. Further derivatization significantly decr eases the Fgn clottability. The addition of up to 5 PEG/Fgn has little, if any, effect on the kinetics of degradation by plasmin. The results suggest that limited modification of Fgn with lysine-reactive PEG allows therapeuti c enhancement of fibrin glues. (C) 2001 John Wiley & Sons, Inc.