Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone.
Postoperative peritoneal adhesions cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized an injectable hydrogel composed of cross-linkable modified hyaluronic acids (HAs) conjugated to dexamethasone (HAX-DEX), and investigated its anti-inflammatory function. HAX-DEX formed a hydrogel in <1min by cross-linking reactions between aldehyde groups and hydrazide groups. The hydrogel degraded in media over 5 days, releasing dexamethasone slowly over that time, reducing TNF-alpha and IL-6 production from lipopolysaccharide-stimulated primary mouse macrophages in vitro. HAX-DEX was biocompatible on subcutaneous injection, and caused less inflammation than unmodified cross-linked HA.
Ito
Taichi
T
Department of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton Street, Cambridge, MA 02142, USA.
Fraser
Iain P
IP
Yeo
Yoon
Y
Highley
Christopher B
CB
Bellas
Evangelia
E
Kohane
Daniel S
DS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008422:Materials Testing; D051379:Mice; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D003432:Cross-Linking Reagents; D016207:Cytokines; D004337:Drug Carriers; D020100:Hydrogels; D003907:Dexamethasone; D006820:Hyaluronic Acid