Abstract:
:Two vinyl sulfone functionalized crosslinkers were developed for the purpose of preparing degradable poly(ethylene glycol) (PEG) hydrogels (EMXL and GABA-EMXL hydrogels). A self-elimination degradation mechanism in which an N-terminal residue of a glutamine is converted to pyroglutamic acid with subsequent release of diamino PEG (DAP) is proposed. The hydrogels were formed via Michael addition by mixing degradable or nondegradable crosslinkers and copolymer {4% w/v; poly[PEG-alt-poly(mercapto-succinic acid)]} at room temperature in phosphate buffer (PB, pH = 7.4). Hydrogel degradation was characterized by assessing diamino PEG release and examining morphological changes as well as the swelling and weight loss ratio under physiological conditions (37 degrees C). Degradation of EMXL and GABA-EMXL hydrogels occurred by surface erosion (confirmed by SEM). GABA-EMXL degradation was significantly faster (approximately 3-fold) than EMXL; however, the degradation of both hydrogels in mouse plasma was 12-times slower than in PBS. The slower degradation rate in plasma as compared to buffer is consistent with the presence of gamma-glutamyltransferase, gamma-glutamylcyclotransferase and/or glutaminyl cyclase (QC), which have been shown to suppress pyroglutamic acid formation. The current studies suggest that EMXL and GABA-EMXL hydrogels may have biomedical applications where 1-2 week degradation timeframes are optimal.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Deshmukh M,Singh Y,Gunaseelan S,Gao D,Stein S,Sinko PJdoi
10.1016/j.biomaterials.2010.05.021subject
Has Abstractpub_date
2010-09-01 00:00:00pages
6675-84issue
26eissn
0142-9612issn
1878-5905pii
S0142-9612(10)00639-3journal_volume
31pub_type
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