Polymeric alginate nanoparticles containing the local anesthetic bupivacaine

Abstract

Bupivacaine (BVC; S75–R25, NovaBupi^®) is an amide-type local anesthetic. Sodium alginate is a water-soluble linear polysaccharide. The present study reports the development of alginate/bis(2-ethylhexyl) sulfosuccinate (AOT) and alginate/chitosan nanoparticle formulations containing BVC (0.5%). The amounts of BVC associated in the alginate/AOT and alginate/chitosan nanoparticles were 87 ± 1.5 and 76 ± 0.9%, respectively. The average diameters and zeta potentials of the nanoparticles were measured for 30 days, and the results demonstrated the good stability of these particles in solution. The in vitro release kinetics showed a different behavior for the release profile of BVC in solution, compared with BVC-loaded alginate nanoparticles. In vitro and in vivo assays showed that alginate–chitosan BVC (BVC_ALG–CHIT) and alginate–AOT BVC (BVC_ALG–AOT) presented low cytotoxicity in 3T3-fibroblasts, enhanced the intensity, and prolonged the duration of motor and sensory blockades in a sciatic nerve blockade model.

Keywords::

• Bupivacaine
• polymeric nanoparticles
• alginate
• in vivo
• in vitro

Acknowledgements

We also thank Cristália Prod. Quím. Farmac. Ltda for the donation of NovaBupi^®.

Declaration of interest

The authors thank FAPESP (06/00121-9), CNPq, and FUNDUNESP for the financial support and studentships provided to R.G. and N.F.S.M. (processes 07/00127-0, 06/00121-9, and 08/01222-9).