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

Author(s):Show less -

Saia Cereda, Cintia Maria ^[1] ; Mecatti, Daniel Sebbe ^[2] ; Boava Papini, Juliana Zampoli ^[1] ; Bueno, Diego Valerio ^[2] ; Franz-Montan, Michelle ^[3] ; Rocha, Thalita ^[2] ; Pedrazzoli Junior, Jose ^[2] ; de Paula, Eneida ^[4] ; de Araujo, Daniele Ribeiro ^[5] ; Grillo, Renato ^[6] ; Fraceto, Leonardo Fernandes ^[7] ; Calafatti, Silvana Aparecida ^[2] ; Tofoli, Giovana Radomille ^[1]

Affiliation

^[1] Inst & Res Ctr Sao Leopoldo Mandic, Rua Jose Rocha Junqueira 13, BR-1304575 Campinas, SP - Brazil

^[2] Sao Francisco Univ, UNIFAG, Braganca Paulista, SP - Brazil

^[3] Univ Estadual Campinas, Dept Physiol Sci, Piracicaba, SP - Brazil

^[4] Univ Estadual Campinas, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[5] Fed Univ ABC, Human & Nat Sci Ctr, Santo Andre, SP - Brazil

^[6] Sao Paulo State Univ UNESP, Sch Engn, Dept Phys & Chem, Ilha Solteira, SP - Brazil

^[7] Sao Paulo State Univ UNESP, Dept Environm Engn, Sorocaba, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PAIN RESEARCH; v. 11, p. 683-691, 2018.
• Web of Science Citations: 2

Abstract

Objective: This study reports a preclinical evaluation of an alginate/chitosan nanoparticle formulation containing NovaBupi (R), 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 (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 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. (AU)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants