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 i...

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Bibliographic Details
Published in:	Biomaterials 2004-08, Vol.25 (19), p.4797-4804
Main Authors:	Jia, Xinqiao, Colombo, Gaia, Padera, Robert, Langer, Robert, Kohane, Daniel S.
Format:	Article
Language:	eng
Subjects:	Animal model Animals Biocompatibility Bupivacaine - administration & dosage Bupivacaine - chemistry Cross-Linking Reagents - chemistry Diffusion Dose-Response Relationship, Drug Hyaluronic acid Hyaluronic Acid - adverse effects Hyaluronic Acid - chemistry Hydrogels - adverse effects Hydrogels - chemistry Male Materials Testing Muscle Nerve Nerve Block - adverse effects Nerve Block - methods Pharmaceutical Vehicles - chemistry Rats Rats, Sprague-Dawley Sciatic Nerve - drug effects Sciatic Nerve - pathology Sciatic Nerve - physiology
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Summary:	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.
ISSN:	0142-9612 1878-5905