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Int J Pharm ; 468(1-2): 152-7, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24726301

RESUMEN

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 48 h. Following surgery, motor block was observed for 48 h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48 h). 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 48 h.


Asunto(s)
Anestésicos Locales/farmacología , Bupivacaína/farmacología , Umbral del Dolor/efectos de los fármacos , Dolor Postoperatorio/prevención & control , Nervio Ciático/efectos de los fármacos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/química , Animales , Conducta Animal/efectos de los fármacos , Bupivacaína/administración & dosificación , Bupivacaína/química , Aceite de Ricino/análogos & derivados , Aceite de Ricino/química , Química Farmacéutica , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Masculino , Actividad Motora/efectos de los fármacos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/fisiopatología , Poliésteres/química , Ratas Sprague-Dawley , Nervio Ciático/fisiopatología , Nervio Ciático/cirugía , Solubilidad , Tecnología Farmacéutica/métodos
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