Toxicogenomic analysis of a sustained release local anesthetic delivery system
Name
nihms353743.pdf
Description
Accepted version
Size
2 MB
Format
Adobe PDF
Checksum (MD5)
d23af1a02c87109650d04ebe3cdfda68
Author(s)
Shichor, Iris
Shomron, Noam
Lawlor, Michael W
Bae, Seul A
Zoldan, Janet
Langer, Robert
Kohane, Daniel S
Date Issued
2012
Journal
Biomaterials
Publisher
Elsevier BV
Citation
Shichor, I., et al. "Toxicogenomic Analysis of a Sustained Release Local Anesthetic Delivery System." Biomaterials 33 13 (2012): 3586-93.
Version
Author's final manuscript
Abstract
Concerns over neurotoxicity have impeded the development of sustained release formulations providing prolonged duration local anesthesia (PDLA) from a single injection, for which there is an urgent clinical need. Here, we have used toxicogenomics to investigate whether nerve injury occurred during week-long continuous sciatic nerve blockade by microspheres containing bupivacaine, tetrodotoxin, and dexamethasone (TBD). Animals treated with amitriptyline solution (our positive control for local anesthetic-associated nerve injury) developed irreversible nerve blockade, had severely abnormal nerve histology, and the expression of hundreds of genes was altered in the dorsal root ganglia at 4 and 7 days after injection. In marked contrast, TBD-treated nerves reverted to normal function, were normal histologically and there were changes in the expression of a small number of genes. Toxicogenomic studies have great potential in delineating patterns of gene expression associated with specific patterns of tissue injury (e.g. amitriptyline neurotoxicity), and in identifying related changes in gene expression upon exposure to a drug, biomaterial, or drug delivery system. © 2012 Elsevier Ltd.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2012.01.043
