Abstract
Purpose
Liposomal formulations of local anesthetics (LA) are able to control drug-delivery in biological systems, prolonging their anesthetic effect. This study aimed to prepare, characterize and evaluatein vivo drug-delivery systems, composed of large unilamellar liposomes (LUV), for bupivacaine (BVC) and mepivacaine (MVC).
Methods
BVC and MVC hydrochloride were encapsulated into LUV (0.4 μm) composed of egg phosphatidylcholine, cholesterol and α-tocopherol (4:3:0.07 molar ratio) to final concentrations of 0.125, 0.25, 0.5% for BVC and 0.5, 1, 2% for MVC. Motor function and antinociceptive effects were evaluated by sciatic nerve blockade induced by liposomal and plain formulations in mice.
Results
Liposomal formulations modified neither the intensity nor the duration of motor blockade compared to plain solutions. Concerning sensory blockade, liposomal BVC (BVCLUV) showed no advantage relatively to the plain BVC injection while liposomal MVC (MVCLUV) improved both the intensity (1.4–1.6 times) and the duration of sensory blockade (1.3–1.7 times) in comparison to its plain solution (P < 0.001) suggesting an increased lipid solubility, availability and controlled-release of the drug at the site of injection.
Conclusion
MVCLUV provided a LA effect comparable to that of BVC. We propose MVCLUV drug delivery as a potentially new therapeutic option for the treatment of acute pain since the formulation enhances the duration of sensory blockade at lower concentrations than those of plain MVC.
Résumé
Objectif
Des préparations liposomales d’anesthésiques locaux (AL) peuvent contrôler l’administration de médicaments dans les systèmes biologiques, prolongeant leur effet anesthésique. Notre objectif était de préparer, caractériser et évaluer des systèmes d’administration de médicaments in vivo, composés de gros liposomes unilamellaires (GLU), pour la bupivacaïne (BVC) et la mépivacaïne (MVC).
Méthode
Le chlorhydrate de BVC et de MVC a été mis en capsules dans des GLU (0,4 μm) composés de lécithine d’œuf, de cholestérol et de α-tocophérol (concentration molaire 4:3:0,07) pour obtenir des concentrations finales de 0,125, 0,25, 0,5 % pour la BVC et 0,5, 1, 2 % pour la MVC. La fonction motrice et les effets antinociceptifs ont été évalués par le blocage du nerf sciatique induit par des préparations liposomales et des préparations simples chez des souris.
Résultats
Les préparations liposomales, comparées aux préparations simples, n’ont pas modifié l’intensité ni la duré du bloc moteur. Quant au bloc sensitif, la BVC liposomale (BVCLUV) n’a pas présenté d’avantage par rapport à l’injection de BVC simple tandis que la MVC liposomale (MVCLUV) a amélioré l’intensité (1,4–1,6 fois) et la duré du bloc sensitif (1,3–1,7 fois) comparée à la solution simple (P < 0,001). Ce qui laisse croire à une meilleure solubilité lipidique, à une disponibilité accrue et à une meilleure administration du médicament à libération contrôlée au site de l’injection.
Conclusion
La MVCLUV fournit un effet AL comparable à celui de la BVC. Nous proposons l’administration de MVCLUV comme un nouveau choix possible de traitement de la douleur aiguë, puisque la préparation augmente la durée du bloc sensitif à des concentrations plus faibles que celles de la MVC simple.
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D.R. de Araujo is the recipient of a fellowship from CAPES (Comissão de Aperfeiçoamento de Pessoal do Ensino Superior) and E. de Paula of a research fellowship from CNPq.
This work was also supported by FAPESP (Proc. 96/04159-8, 01/12476-2).
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de Araujo, D.R., Cereda, C.M.S., Brunetto, G.B. et al. Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice. Can J Anesth 51, 566–572 (2004). https://doi.org/10.1007/BF03018399
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DOI: https://doi.org/10.1007/BF03018399