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

Abstract

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 (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.

Results

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.

Conclusion

The encapsulation of BVC prolongs the local anesthetic effect after infraorbital nerve blockade and altered the pharmacokinetics after intrathecal injection.