Physical Polymer Matrices Based on Affinity Interactions between Peptides and Polysaccharides

Abstract

A rapidly forming polymer matrix with affinity-based controlled release properties was developed based upon interactions between heparin-binding peptides and heparin. Dynamic mechanical testing of 10% (w/v) compositions consisting of a 3:1 molar ratio of poly(ethylene glycol)-co-peptide (approximately 18,000 g/mol) to heparin (approximately 18,000 g/mol) revealed a viscoelastic profile similar to that of concentrated, large molecular weight polymer solutions and melts. In addition, the biopolymer mixtures recovered quickly following thermal denaturation and mechanical insult. These gel-like materials were able to sequester exogenous heparin-binding peptides and could release these peptides over several days at rates dependent on relative heparin affinity. The initial release rates ranged from 3.3% per hour for a peptide with low heparin affinity to 0.025% per hour for a peptide with strong heparin affinity. By altering the affinity of peptides to heparin, a series of peptides can be developed to yield a range of release profiles useful for controlled in vivo delivery of therapeutics.

Manipulation of hydrogel assembly and growth factor delivery via the use of peptide–polysaccharide interactions

“…As shown in the figure, both gels show a burst release of approximately 25%, followed by a nearly linear slow release of bFGF over 10 days, to a maximum measured release of 35-40%. This initial release is similar to the initial burst release of some heparin-binding peptides from physically crosslinked, heparincontaining hydrogels [12]. The bFGF is released slightly more quickly from the PEG-LMWH controls than from the PEG-LMWH/PEG-PF4 ZIP hydrogels, despite the slightly higher ratio of LMWH: bFGF in the control samples.…”

“…The fact that the PF4 ZIP peptide also binds strongly to heparin was confirmed via affinity chromatography and SPR experiments. The use of a smaller peptide with potent heparin binding affinity may permit more facile synthesis of active bioconjugates and assembly of hydrogels, as previously demonstrated [10][11][12].…”

“…Accordingly, heparin has been incorporated into covalent hydrogel delivery systems because of this ability to bind a diverse set of proteins. In addition, we and others have demonstrated that the interactions between heparin and specific HBPs can also mediate the assembly of noncovalently associated hydrogel networks [10][11][12].…”

“…The PEG-LWMH/PEG-HIP hydrogel (LMWH:HIP=8:2) data are adapted from Ref. [12]. The errors are derived from the average of duplicate measurements.…”

“…(Complete sets of bFGF release and hydrogel erosion data for the PEG-LMWH/ PEG-HIP hydrogels are adapted from Ref. [12] and are compared to those of the PEG-LMWH/ PEG-PF4 ZIP hydrogels in Figs. A4 and A5.)…”