Toxicogenomic analysis of a sustained release local anesthetic delivery system
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 w...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/134468 |
| _version_ | 1826191231567265792 |
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| author | Shichor, Iris Shomron, Noam Lawlor, Michael W Bae, Seul A Zoldan, Janet Langer, Robert Kohane, Daniel S |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Shichor, Iris Shomron, Noam Lawlor, Michael W Bae, Seul A Zoldan, Janet Langer, Robert Kohane, Daniel S |
| author_sort | Shichor, Iris |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:52:40Z |
| format | Article |
| id | mit-1721.1/134468 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:52:40Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1344682023-03-01T20:20:13Z Toxicogenomic analysis of a sustained release local anesthetic delivery system Shichor, Iris Shomron, Noam Lawlor, Michael W Bae, Seul A Zoldan, Janet Langer, Robert Kohane, Daniel S Harvard University--MIT Division of Health Sciences and Technology Koch Institute for Integrative Cancer Research at MIT 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. 2021-10-27T20:05:08Z 2021-10-27T20:05:08Z 2012 2019-09-04T17:48:49Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134468 Shichor, I., et al. "Toxicogenomic Analysis of a Sustained Release Local Anesthetic Delivery System." Biomaterials 33 13 (2012): 3586-93. en 10.1016/j.biomaterials.2012.01.043 Biomaterials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Shichor, Iris Shomron, Noam Lawlor, Michael W Bae, Seul A Zoldan, Janet Langer, Robert Kohane, Daniel S Toxicogenomic analysis of a sustained release local anesthetic delivery system |
| title | Toxicogenomic analysis of a sustained release local anesthetic delivery system |
| title_full | Toxicogenomic analysis of a sustained release local anesthetic delivery system |
| title_fullStr | Toxicogenomic analysis of a sustained release local anesthetic delivery system |
| title_full_unstemmed | Toxicogenomic analysis of a sustained release local anesthetic delivery system |
| title_short | Toxicogenomic analysis of a sustained release local anesthetic delivery system |
| title_sort | toxicogenomic analysis of a sustained release local anesthetic delivery system |
| url | https://hdl.handle.net/1721.1/134468 |
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