+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          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.


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

          Related collections

          Most cited references 30

          • Record: found
          • Abstract: found
          • Article: not found

          Anti-inflammatory properties of local anesthetics and their present and potential clinical implications.

          Development of new local anesthetic agents has been focused on the potency of their nerve-blocking effects, duration of action and safety and has resulted in a substantial number of agents in clinical use. It is well established and well documented that the nerve blocking effects of local anesthetics are secondary to their interaction with the Na+ channels thereby blocking nerve membrane excitability and the generation of action potentials. Accumulating data suggest however that local anesthetics also possess a wide range of anti-inflammatory actions through their effects on cells of the immune system, as well as on other cells, e.g. microorganisms, thrombocytes and erythrocytes. The potent anti-inflammatory properties of local anesthetics, superior in several aspects to traditional anti-inflammatory agents of the NSAID and steroid groups and with fewer side-effects, has prompted clinicians to introduce them in the treatment of various inflammation-related conditions and diseases. They have proved successful in the treatment of burn injuries, interstitial cystitis, ulcerative proctitis, arthritis and herpes simplex infections. The detailed mechanisms of action are not fully understood but seem to involve a reversible interaction with membrane proteins and lipids thus regulating cell metabolic activity, migration, exocytosis and phagocytosis.
            • Record: found
            • Abstract: found
            • Article: not found

            A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty.

            DepoFoam bupivacaine is a novel liposomal formulation of bupivacaine designed to provide prolonged postsurgical analgesia. This dose-ranging study evaluated extent and duration of analgesia following administration of DepoFoam bupivacaine in patients undergoing total knee arthroplasty (TKA). Efficacy, safety, and pharmacokinetics of DepoFoam bupivacaine doses of 133, 266, 399, or 532 mg were compared with bupivacaine HCl (150 mg) with epinephrine given as single injections via wound infiltration in TKA patients (N=138). Primary efficacy measure was AUC of pain intensity scores assessed by numeric rating scale with activity (NRS-A) through Day 4 postsurgery. Other assessments included pain intensity at rest (NRS-R), postsurgical opioid consumption, and safety, among others. Mean AUC of NRS-A scores through Day 4 were 20.7, 19.5, 18.8, and 19.1 for the 133-mg, 266-mg, 399-mg, and 532-mg DepoFoam bupivacaine groups vs 20.4 for bupivacaine HCl. With DepoFoam bupivacaine 532-mg, differences in NRS-R scores reached statistical significance (P<0.05) vs bupivacaine HCl on Days 1 and 5 and mean AUC NRS-R scores were significantly lower through Days 2-5; a dose-response trend was demonstrated. Mean rating for blinded care provider's satisfaction with analgesia was significantly higher for DepoFoam bupivacaine 532 mg vs bupivacaine HCl (P ≤ 0.05). Other efficacy measures showed no statistically significant differences. Exposure to bupivacaine increased in a dose-related manner, as reflected by mean and maximum plasma bupivacaine concentrations, and AUC(0-∞). Treatment with DepoFoam bupivacaine 532 mg was associated with statistically significantly greater analgesia while patients were at rest after surgery compared with bupivacaine HCl. Copyright © 2011. Published by Elsevier B.V.
              • Record: found
              • Abstract: found
              • Article: not found

              Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

              Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                06 April 2018
                : 11
                : 683-691
                [1 ]Institute and Research Center São Leopoldo Mandic, Campinas, São Paulo, Brazil
                [2 ]UNIFAG, São Francisco University, Bragança Paulista, São Paulo, Brazil
                [3 ]Department of Physiological Sciences, University of Campinas, Piracicaba, São Paulo, Brazil
                [4 ]Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, São Paulo, Brazil
                [5 ]Human and Natural Science Centre, Federal University of ABC, Santo André, São Paulo, Brazil
                [6 ]Department of Physics and Chemistry, School of Engineering, São Paulo State University (UNESP), Ilha Solteira, São Paulo, Brazil
                [7 ]Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, São Paulo, Brazil
                Author notes
                Correspondence Giovana Radomille Tofoli, Institute and Research Center São Leopoldo Mandic, Rua José Rocha Junqueira 13, 13045-75, Campinas, São Paulo, Brazil, Email giovana.tofoli@ 123456slmandic.edu.br
                © 2018 Cereda et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research


                Comment on this article