Prolongation of sciatic nerve blockade by in situ cross-linked hyaluronic acid

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% 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. (C) 2003 Elsevier Ltd. All rights reserved.