Extended duration local anesthetic agent in a rat paw model
[Display omitted] Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation – 15% bupivacaine in poly(DL-lacti...
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Veröffentlicht in: | International journal of pharmaceutics 2014-07, Vol.468 (1-2), p.152-157 |
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creator | Ickowicz, D.E. Golovanevski, L. Domb, A.J. Weiniger, C.F. |
description | [Display omitted]
Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation – 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave’s hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48h. Following surgery, motor block was observed for 48h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48h. |
doi_str_mv | 10.1016/j.ijpharm.2014.04.022 |
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Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation – 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave’s hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48h. Following surgery, motor block was observed for 48h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48h.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2014.04.022</identifier><identifier>PMID: 24726301</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anesthetics, Local - administration & dosage ; Anesthetics, Local - chemistry ; Anesthetics, Local - pharmacology ; Animals ; Behavior, Animal - drug effects ; Bupivacaine ; Bupivacaine - administration & dosage ; Bupivacaine - chemistry ; Bupivacaine - pharmacology ; Castor Oil - analogs & derivatives ; Castor Oil - chemistry ; Chemistry, Pharmaceutical ; Delayed-Action Preparations ; Disease Models, Animal ; Injectable local anesthetics ; Male ; Motor Activity - drug effects ; Pain Threshold - drug effects ; Pain, Postoperative - etiology ; Pain, Postoperative - physiopathology ; Pain, Postoperative - prevention & control ; Polyesters - chemistry ; Polymer ; Prolonged release ; Rats, Sprague-Dawley ; Sciatic Nerve - drug effects ; Sciatic Nerve - physiopathology ; Sciatic Nerve - surgery ; Solubility ; Technology, Pharmaceutical - methods</subject><ispartof>International journal of pharmaceutics, 2014-07, Vol.468 (1-2), p.152-157</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-a2e4f2ebf336003f35610147a2738915d93267d5067eec720406255a618735783</citedby><cites>FETCH-LOGICAL-c365t-a2e4f2ebf336003f35610147a2738915d93267d5067eec720406255a618735783</cites><orcidid>0000-0002-2241-7726</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2014.04.022$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24726301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ickowicz, D.E.</creatorcontrib><creatorcontrib>Golovanevski, L.</creatorcontrib><creatorcontrib>Domb, A.J.</creatorcontrib><creatorcontrib>Weiniger, C.F.</creatorcontrib><title>Extended duration local anesthetic agent in a rat paw model</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation – 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave’s hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48h. Following surgery, motor block was observed for 48h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48h.</description><subject>Anesthetics, Local - administration & dosage</subject><subject>Anesthetics, Local - chemistry</subject><subject>Anesthetics, Local - pharmacology</subject><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Bupivacaine</subject><subject>Bupivacaine - administration & dosage</subject><subject>Bupivacaine - chemistry</subject><subject>Bupivacaine - pharmacology</subject><subject>Castor Oil - analogs & derivatives</subject><subject>Castor Oil - chemistry</subject><subject>Chemistry, Pharmaceutical</subject><subject>Delayed-Action Preparations</subject><subject>Disease Models, Animal</subject><subject>Injectable local anesthetics</subject><subject>Male</subject><subject>Motor Activity - drug effects</subject><subject>Pain Threshold - drug effects</subject><subject>Pain, Postoperative - etiology</subject><subject>Pain, Postoperative - physiopathology</subject><subject>Pain, Postoperative - prevention & control</subject><subject>Polyesters - chemistry</subject><subject>Polymer</subject><subject>Prolonged release</subject><subject>Rats, Sprague-Dawley</subject><subject>Sciatic Nerve - drug effects</subject><subject>Sciatic Nerve - physiopathology</subject><subject>Sciatic Nerve - surgery</subject><subject>Solubility</subject><subject>Technology, Pharmaceutical - methods</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLAzEUhYMoWqs_QcnSzdQ8JskUFyKlPqDgRtchTe7YDPMymfHx701pdStcuJvv3HvOQeiCkhklVF5XM1_1GxOaGSM0n5E0jB2gCS0Uz3iu5CGaEK6KTFDFT9BpjBUhRDLKj9EJyxWTnNAJull-DdA6cNiNwQy-a3HdWVNj00IcNjB4i80btAP2LTY4Ibg3n7jpHNRn6Kg0dYTz_Z6i1_vly-IxWz0_PC3uVpnlUgyZYZCXDNYl55IQXnIhU4JcGaZ4MafCzTmTygkiFYBVjOTJphBGbqMIVfAputrd7UP3PiZbuvHRQl0nj90YNRVsXuRMSZZQsUNt6GIMUOo--MaEb02J3vamK73vTW970yQN2-ou9y_GdQPuT_VbVAJudwCkoB8ego7WQ2vB-QB20K7z_7z4AT3qfkQ</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Ickowicz, D.E.</creator><creator>Golovanevski, L.</creator><creator>Domb, A.J.</creator><creator>Weiniger, C.F.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2241-7726</orcidid></search><sort><creationdate>20140701</creationdate><title>Extended duration local anesthetic agent in a rat paw model</title><author>Ickowicz, D.E. ; Golovanevski, L. ; Domb, A.J. ; Weiniger, C.F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-a2e4f2ebf336003f35610147a2738915d93267d5067eec720406255a618735783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Anesthetics, Local - administration & dosage</topic><topic>Anesthetics, Local - chemistry</topic><topic>Anesthetics, Local - pharmacology</topic><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Bupivacaine</topic><topic>Bupivacaine - administration & dosage</topic><topic>Bupivacaine - chemistry</topic><topic>Bupivacaine - pharmacology</topic><topic>Castor Oil - analogs & derivatives</topic><topic>Castor Oil - chemistry</topic><topic>Chemistry, Pharmaceutical</topic><topic>Delayed-Action Preparations</topic><topic>Disease Models, Animal</topic><topic>Injectable local anesthetics</topic><topic>Male</topic><topic>Motor Activity - drug effects</topic><topic>Pain Threshold - drug effects</topic><topic>Pain, Postoperative - etiology</topic><topic>Pain, Postoperative - physiopathology</topic><topic>Pain, Postoperative - prevention & control</topic><topic>Polyesters - chemistry</topic><topic>Polymer</topic><topic>Prolonged release</topic><topic>Rats, Sprague-Dawley</topic><topic>Sciatic Nerve - drug effects</topic><topic>Sciatic Nerve - physiopathology</topic><topic>Sciatic Nerve - surgery</topic><topic>Solubility</topic><topic>Technology, Pharmaceutical - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ickowicz, D.E.</creatorcontrib><creatorcontrib>Golovanevski, L.</creatorcontrib><creatorcontrib>Domb, A.J.</creatorcontrib><creatorcontrib>Weiniger, C.F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ickowicz, D.E.</au><au>Golovanevski, L.</au><au>Domb, A.J.</au><au>Weiniger, C.F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extended duration local anesthetic agent in a rat paw model</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>468</volume><issue>1-2</issue><spage>152</spage><epage>157</epage><pages>152-157</pages><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation – 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave’s hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48h. Following surgery, motor block was observed for 48h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48h.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24726301</pmid><doi>10.1016/j.ijpharm.2014.04.022</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-2241-7726</orcidid></addata></record> |
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subjects | Anesthetics, Local - administration & dosage Anesthetics, Local - chemistry Anesthetics, Local - pharmacology Animals Behavior, Animal - drug effects Bupivacaine Bupivacaine - administration & dosage Bupivacaine - chemistry Bupivacaine - pharmacology Castor Oil - analogs & derivatives Castor Oil - chemistry Chemistry, Pharmaceutical Delayed-Action Preparations Disease Models, Animal Injectable local anesthetics Male Motor Activity - drug effects Pain Threshold - drug effects Pain, Postoperative - etiology Pain, Postoperative - physiopathology Pain, Postoperative - prevention & control Polyesters - chemistry Polymer Prolonged release Rats, Sprague-Dawley Sciatic Nerve - drug effects Sciatic Nerve - physiopathology Sciatic Nerve - surgery Solubility Technology, Pharmaceutical - methods |
title | Extended duration local anesthetic agent in a rat paw model |
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