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
Hauptverfasser: Ickowicz, D.E., Golovanevski, L., Domb, A.J., Weiniger, C.F.
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container_end_page 157
container_issue 1-2
container_start_page 152
container_title International journal of pharmaceutics
container_volume 468
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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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). 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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. 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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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