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Type: Artigo de periódico
Title: Drug-delivery Systems For Racemic Bupivacaine (s50-r50) And Bupivacaine Enantiomeric Mixture (s75-r25): Cyclodextrins Complexation Effects On Sciatic Nerve Blockade In Mice [sistemas De Liberação Controlada Com Bupivacaína Racêmica (s50-r50) E Mistura Enantiomérica De Bupivacaína (s75-r25): Efeitos Da Complexaćão Com Ciclodextrinas No Bloqueio Do Nervo Ciático Em Camundongos]
Author: Ribeiro De Araujo D.
Fernandes Fraceto L.
De Assuncao Braga A.D.F.
De Paula E.
Abstract: BACKGROUND AND OBJECTIVES: Bupivacaine-induced side effects have led to the search for new local anesthetics (LA) with similar potency and lower toxicity, such as bupivacaine enantiomeric mixture (S75-R25). Drug-delivery systems for LA in carriers, such as cyclodextrins (CD), have been developed to improve anesthetic potency and therapeutic index of those drugs. This study aimed at preparing, characterizing and evaluating the anesthetic efficacy of inclusion complexes of bupivacaine enantiomeric mixture (S75-R25) and racemic bupivacaine (S50-R50) with hydroxypropylβ- cyclodextrin (HPβ-CD) comparing them to clinically available preparations. METHODS: Inclusion complexes were obtained by mixing appropriate volumes of HPβ-CD and S50-R50 or S75-R25 to final 1:1 or 1:2 molar ratios and were characterized by phase solubility experiments. Affinity constants (K) were determined between HPβ-CO and each LA. Motor and sensory blocks induced by plain or complexed LA formulations were evaluated in mice by sciatic nerve block. Three LA concentrations were used during the experiment: 0.125, 0.25 and 0.5%. RESULTS: Solubility experiments results were indicative of S50-R50:HPβ-CD and S75-R25:HPβ-CD complexation, with similar affinity constant (K) values: 14.7 M -1 and 14.3 M -1, respectively. In vivo experiments have shown that complexation has enhanced differential nerve blockade induced by LA: i) motor blockade duration induced by S75-R25 was similar, to the induced by but less intense S50-R50 (p < 0.001). S50-R50 HPβ-CD and S75-R25 HPβ-CD complexes have decreased onset (p < 0.01 and p < 0.05. respectively), without changing motor block intensity (E max) as compared to plain drugs; ii) sensory block evaluation has revealed higher analgesic intensity with S50-R50 HPβ-CD (2-fold, p < 0.001) and S75-R25 HPβ-CD (1.5-1.8-fold, p < 0.01 and p < 0.001, respectively) with both molar ratios (1:1 and 1:2, LA:CD), in addition to prolonging analgesic effect as compared to S50-R50 and S75-R25. CONCLUSIONS: More pronounced analgesic effects obtained by complexation with HPβ-CD have shown that both formulations. S50-R50 HPβ-CD, are S75-R25 HPβ-CD, are very useful for postoperative pain relief, requiring lower LA concentrations. Nevertheless, it is worth noticing that S75-R25 - being less toxic than racemic bupivacaine - is an interesting alternative for the development of more effective and safe drug-delivery systems as compared to racemic bupivacaine (S50-R50). © Sociedade Brasileira de Anestesiologia, 2005.
Rights: fechado
Identifier DOI: 
Date Issue: 2005
Appears in Collections:Unicamp - Artigos e Outros Documentos

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