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 Tofoli 1
06 April 2018
This study reports a preclinical evaluation of an alginate/chitosan nanoparticle formulation containing NovaBupi®, a racemic bupivacaine (BVC) containing 25% dextrobupivacaine and 75% levobupivacaine.
New Zealand White rabbits (n=6) received intraoral or intrathecal injections of BVC 0.5% or BVC 0.5%-loaded alginate–chitosan nanoparticles (BVC ALG). 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 (NP ALG). Histological evaluation of local toxicity after 6 hours and 24 hours of the treatments was performed in rats’ (n=6) oral tissues.
No statistically significant difference was observed between plasma concentrations and pharmacokinetic parameters ( p>0.05) after intraoral injections. However, after intrathecal injection BVC ALG changed approximately three times the values of volume of distribution and area under the curve (AUC 0–t; p<0.05). The total analgesic effect of BVC after infraorbital nerve blockade was improved by 1.4-fold ( p<0.001) with BVC ALG. BVC and BVC ALG did not induce significant local inflammatory reaction.