title: Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 45 Carleton Street, Cambridge, MA 02142, USA.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ito
authors.forename: Iain P
authors.initials: IP
authors.lastname: Fraser
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Highley
authors.forename: Evangelia
authors.initials: E
authors.lastname: Bellas
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D003432:Cross-Linking Reagents; D016207:Cytokines; D004337:Drug Carriers; D020100:Hydrogels; D003907:Dexamethasone; D006820:Hyaluronic Acid