Premium
Covalent incorporation and controlled release of active dexamethasone from injectable polyethylene glycol hydrogels
Author(s) -
Bezuidenhout Deon,
Oosthuysen Anel,
Davies Neil,
Ahrenstedt Lage,
Dobner Stephan,
Roberts Peter,
Zilla Peter
Publication year - 2013
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34438
Subject(s) - self healing hydrogels , polyethylene glycol , swelling , dexamethasone , materials science , drug delivery , covalent bond , polymer chemistry , kinetics , acrylate , organic chemistry , chemistry , polymer , nanotechnology , composite material , copolymer , medicine , quantum mechanics , endocrinology , physics
Dexamethasone (Dex) is used in a wide range of applications, but may have undesirable systemic side effects. A number of techniques have thus been developed to deliver the substance locally. In this study, dexamethasone was acrylated, pegylated, and tethered to hydrolytically degradable (acrylate based) and nondegradable (vinyl sulfone based) polyethylene glycol hydrogels by nucleophilic addition. Hydrogel swelling, drug elution and drug activity were followed over an extended period in vitro . Nondegradable gels were stable for more than a year, while degradable gels showed increasing swelling ratios due to degradation that resulted in disintegration after ∼12 days. Near‐linear (zero order) release could be achieved in some cases with the degradable gels, while release from the nondegradable gels approximated first order initial release kinetics. Significantly delayed release was observed in all cases where the Dex was linked to the gels, when compared with controls where the drug was merely physically incorporated. Eluates from the gels containing the tethered drug showed high levels of activity for extended time periods, while the activity of the eluates from gels containing nonbound dexamethasone decreased rapidly within the first few days. Dexamethasone can thus be incorporated using nucleophilic addition chemistry to produce gels that are capable of sustained release of the active drug. The methodology is applicable to a variety of drugs that contain hydroxyl groups. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.