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P Pu ur rp po os se e: : 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 evaluate in vivo drug-delivery systems, composed of large unilamellar liposomes (LUV), for bupivacaine (BVC) and mepivacaine (MVC).M Me et th ho od ds s: : 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.R Re es su ul lt ts s: : Liposomal formulations modified neither the intensity nor the duration of motor blockade compared to plain solutions. Concerning sensory blockade, liposomal BVC (BVC LUV ) showed no advantage relatively to the plain BVC injection while liposomal MVC (MVC LUV ) 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.C Co on nc cl lu us si io on n: : MVC LUV provided a LA effect comparable to that of BVC. We propose MVC LUV 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. de 0,125, 0,25, 0,5 % pour la BVC et 0,5 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'oeuf, de cholestérol et de α-tocophérol (concentration molaire 4:3:0,07) pour obtenir des concentrations finales

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We assessed the effect of local anesthetics (LA) from different families such as esters (benzocaine), linear aminoamides (lidocaine) and cyclic aminoamides (bupivacaine) on the platelet aggregation induced by ADP. Liposomal formulations of the three LA, prepared with egg phosphatidylcholine:cholesterol alpha-tocopherol, were also tested. The three LA were able to inhibit platelet aggregation induced by ADP, in the following order: bupivacaine > lidocaine > benzocaine. After encapsulation into liposomes the inhibitory effect increased for all anesthetics studied, showing that aggregation tests could be used to assess the toxicity of new drug formulations.

This study describes the encapsulation of the local anaesthetic lidocaine (LDC) in large unilamellar liposomes (LUV) prepared in a scalable procedure, with hydrogenated soybean phosphatidylcholine, cholesterol and mannitol. Structural properties of the liposomes were assessed by dynamic light scattering, nanoparticle tracking analysis and transmission electron microscopy. A modified, two-compartment Franz-cell system was used to evaluate the release kinetics of LDC from the liposomes. The in vivo anaesthetic effect of liposomal LDC 2% (LUV) was compared to LDC 2% solution without (LDC) or with the vasoconstrictor epinephrine (1:100 000) (LDC), in rat infraorbital nerve blockade model. The structural characterization revealed liposomes with spherical shape, average size distribution of 250 nm and low polydispersity even after LDC incorporation. Zeta potential laid around -30 mV and the number of suspended liposomal particles was in the range of 10 vesicles/mL. Also the addition of cryoprotectant (mannitol) did not provoke structural changes in liposomes properties. In vitro release profile of LDC from LUV fits well with a biexponential model, in which the LDC encapsulated (EE% = 24%) was responsible for an increase of 67% in the release time in relation to LDC (p < 0.05). Also, the liposomal formulation prolonged the sensorial nervous blockade duration (∼70 min), in comparison with LDC (45 min), but less than LDC (130 min). In this context, this study showed that the liposomal formulations prepared by scalable procedure were suitable to promote longer and safer buccal anaesthesia, avoiding side effects of the use of vasoconstrictors.

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