title: Prolongation of sciatic nerve blockade by in situ cross-linked hyaluronic acid.
abstract: Controlled release technology has been applied extensively in providing prolonged duration local anesthesia. Here we used modified hyaluronic acids (HAs; hydrazide and aldehyde) that cross-link upon mixing, as the vehicle for bupivacaine. We assessed the formulations' efficacy and biocompatibility in a rat model of sciatic nerve blockade. We found that 2% (w/v) cross-linked HA doubled the duration of block of 0.1%, 0.25%, and 0.5% (w/v) bupivacaine, without a statistically significant increase in myotoxicity. 1% (w/w) cross-linked HA also prolonged nerve block, but unmodified HA, and both modified HAs did not. HA itself was associated with a mild to moderate inflammatory response with macrophages and lymphocytes. Cross-linked HA is an effective and biocompatible vehicle for enhancing local anesthetic efficacy.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
authors.forename: Robert
authors.initials: R
authors.lastname: Padera
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D006820:Hyaluronic Acid / Q000009:adverse effects / Q000737:chemistry*; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D009407:Nerve Block / Q000009:adverse effects / Q000379:methods*; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*
chemical_list: D003432:Cross-Linking Reagents; D020100:Hydrogels; D014677:Pharmaceutical Vehicles; D006820:Hyaluronic Acid; D002045:Bupivacaine