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Bupivacaine in alginate and chitosan nanoparticles: an in vivo evaluation of efficacy, pharmacokinetics, and local toxicity

Authors Cereda CMS, Mecatti DS, Papini JZ, Bueno DV, Franz-Montan M, Rocha T, Pedrazzoli Júnior J, de Paula E, de Araújo DR, Grillo R, Fraceto LF, Calafatti SA, Tofoli GR

Received 2 December 2017

Accepted for publication 17 January 2018

Published 6 April 2018 Volume 2018:11 Pages 683—691

DOI https://doi.org/10.2147/JPR.S158695

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Michael Schatman


Cíntia Maria Saia Cereda,1 Daniel Sebbe Mecatti,2 Juliana Zampoli Boava Papini,1 Diego Valério Bueno,2 Michelle Franz-Montan,3 Thalita Rocha,2 José Pedrazzoli Júnior,2 Eneida de Paula,4 Daniele Ribeiro de Araújo,5 Renato Grillo,6 Leonardo Fernandes Fraceto,7 Silvana Aparecida Calafatti,2 Giovana Radomille Tofoli1

1Institute and Research Center São Leopoldo Mandic, Campinas, São Paulo, Brazil; 2UNIFAG, São Francisco University, Bragança Paulista, São Paulo, Brazil; 3Department of Physiological Sciences, University of Campinas, Piracicaba, São Paulo, Brazil; 4Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, São Paulo, Brazil; 5Human and Natural Science Centre, Federal University of ABC, Santo André, São Paulo, Brazil; 6Department of Physics and Chemistry, School of Engineering, São Paulo State University (UNESP), Ilha Solteira, São Paulo, Brazil; 7Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, São Paulo, Brazil

Objective: This study reports a preclinical evaluation of an alginate/chitosan nanoparticle formulation containing NovaBupi®, a racemic bupivacaine (BVC) containing 25% dextrobupivacaine and 75% levobupivacaine.
Methods: New Zealand White rabbits (n=6) received intraoral or intrathecal injections of BVC 0.5% or BVC 0.5%-loaded alginate–chitosan nanoparticles (BVCALG). BVC plasma levels and pharmacokinetic parameters were determined in blood samples of these rabbits. An infraorbital nerve blockade was performed in male Wistar rats (n=7) with the same formulations and the vehicle (NPALG). Histological evaluation of local toxicity after 6 hours and 24 hours of the treatments was performed in rats’ (n=6) oral tissues.
Results: No statistically significant difference was observed between plasma concentrations and pharmacokinetic parameters (p>0.05) after intraoral injections. However, after intrathecal injection BVCALG changed approximately three times the values of volume of distribution and area under the curve (AUC0–t; p<0.05). The total analgesic effect of BVC after infraorbital nerve blockade was improved by 1.4-fold (p<0.001) with BVCALG. BVC and BVCALG did not induce significant local inflammatory reaction.
Conclusion: The encapsulation of BVC prolongs the local anesthetic effect after infraorbital nerve blockade and altered the pharmacokinetics after intrathecal injection.

Keywords: local anesthetics, bupivacaine, polymeric nanoparticle, drug delivery, preclinical study

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