Protein compatibility of selected cross-linking reactions for hydrogels.
The compatibility of selected cross-linking reactions with lysozyme is investigated. Michael-type additions of nucleophilic amino acids to maleimide, vinyl sulfone and acrylamide groups are detected by gel electrophoresis. The degree of modification depends on the polymer and the pH. Complete modification with more than five PEG chains is observed after incubation with mPEG5k-vinyl sulfone at pH 9, whereas 96% of the protein remains unmodified after incubation with mPEG5k-acrylamide at pH 4. Incubation with mPEG5k-thiol results in thiol-disulfide exchange reactions. Hydrogel preparation is simulated by using polymer mixtures. Protein modifications are detected, which may affect the protein structure, decrease activity and bioavailability, and increase the risk for immune responses.
Department of Pharmaceutical Technology, Faculty of Chemistry and Pharmacy, University of Regensburg, Universitätsstr. 31, 93040, Regensburg, Germany.
Nadine
N
Hammer
Ferdinand P
FP
Brandl
Susanne
S
Kirchhof
Viktoria
V
Messmann
Achim M
AM
Goepferich
D000818:Animals; D002645:Chickens; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D020100:Hydrogels / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
D003432:Cross-Linking Reagents; D020100:Hydrogels; D008301:Maleimides; C043592:maleimide; D011092:Polyethylene Glycols; D009113:Muramidase
compatibility; crosslinking; drug delivery systems; hydrogels; proteins