Abstract
Purpose
A laboratory investigation was undertaken to compare the in vivo antinociceptive effects of 2% liposomal formulations of prilocaine (PLC), lidocaine (LDC) and mepivacaine (MVC) compared to plain solutions of each of these three local anesthetics.
Methods
Large unilamellar vesicles were prepared by extrusion (400 nm), at pH 7.4. The membrane/water partition coefficients were obtained from encapsulation efficiency values, after incorporation of each local anesthetic to the vesicles. The anesthetic effect of each liposomal formulation was compared to the respective local anesthetic solution in water, using the infraorbital nerve-blockade test, in rats.
Results
The partition coefficients were: 57 for PLC, 114 for LDC and 93 for MVC. In vivo results showed that local anesthetic-free liposomes, used as control, had no analgesic effect. In contrast, the encapsulated formulations induced increased intensities of total anesthetic effect (35.3%, 26.1 % and 57.1 %) and time for recovery (percentage increases of 30%, 23.1 % and 56%), respectively, for PLC, LDC and MVC when compared to the plain solutions (P < 0.01).
Conclusions
These results indicate that liposomes provide effective drug-delivery systems for intermediate-duration local anesthetics. Mepivacaine was affected to the greatest extent, while LDC benefited least from liposome encapsulation, possibly due to greater vasodilatory properties of LDC.
Objectif
Une recherche en laboratoire a été entreprise pour comparer les effets antinociceptifs in vivo de préparations liposomiques de prilocaïne (PLC), de lidocaïne (LDC) et de mépivacaïne (MVC) à 2 %, à des solutions simples de chacun de ces anesthésiques locaux.
Méthode
De grandes vésicules unilamellaires ont été préparées par extrusion (400 nm), à un pH de 7,4. Les coefficients de partage membrane/eau ont été obtenus des valeurs d’efficacité de l’encapsulation, après l’introduction de chaque anesthésique local dans les vésicules. L’effet anesthésique de chaque préparation liposomique a été comparé à la solution respective d’anesthésique local dans l’eau par le test de blocage du nerf infra-orbitaire chez des rats.
Résultats
Les coefficients de partage ont été de : 57 pour la PLC, 114 pour la LDC et 93 pour la MVC. Les résultats in vivo ont montré que les liposomes témoins sans anesthésique local n’avaient pas d’effet analgésique. Par contre, les préparations en capsules ont augmenté l’intensité anesthésique totale (35,3 %, 26,1 % et 57,1 %) et le temps de récupération (30 %, 23,1 % et 56 %) respectivement pour la PLC, la LDC et la MVC comparées aux solutions simples (P < 0,01).
Conclusion
Ces résultats indiquent que les liposomes sont des systèmes de vecteurs de médicaments efficaces pour les anesthésiques locaux de durée moyenne. La MVC a surtout bénéficié, et la LDC le moins, de l’encapsulation liposomique, peut-être à cause de ses plus importantes propriétés vasodilatatrices.
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This work was also supported by FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo - 01/12476-2).
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Saia Cereda, C.M., Brunetto, G.B., de Araújo phd, D.R. et al. Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration. Can J Anesth 53, 1092–1097 (2006). https://doi.org/10.1007/BF03022876
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DOI: https://doi.org/10.1007/BF03022876