Th. Barker et al., Modification of fibrinogen with poly(ethylene glycol) and its effects on fibrin clot characteristics, J BIOMED MR, 56(4), 2001, pp. 529-535
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.