Anesthetic efficacy of uni and multilamelar liposomal mepivacaine formulations in infraorbital and inferior alveolar nerve blocks and subcutaneous infiltration in surgical wound, in rats

The aim of this study was to evaluate the anesthetic efficacy of two liposomal (unilamelar and multilamelar, 8mM lipid concentration) mepivacaine formulations compared to mepivacaine with epinephrine in three models: infraorbital nerve block (IONB), inferior alveolar nerve block (IANB) and subcutaneous infiltration in surgical wound (SISW) in rats. In each model animals received one of the following formulations: 2% mepivacaine with 1:100,000 epinephrine, (Mepi-Epi), liposomal unilamelar 3% mepivacaína (Mepi-LUV), liposomal multilamelar 3% mepivacaína (Mepi-MLV), and the respective controls: 0.9% NaCl solution, and liposomal unilamelar and liposomal multilamelar suspensions without the local anesthetic. For IONB (n= 30) and IANB (n= 51) the animals were divided into 3 groups, which received one of the formulations containing mepivacaine in the right side and the respective control formulation in the left side; 0.1 mL and 0.2mL were respectively injected for IONB and IANB. After IONB the success and duration of anesthesia was evaluated by upper lip pinching.After IANB the onset, duration and success of pulpal anesthesia were evaluated by electric stimulus. For SISW experiment the 48 rats were divided into 6 groups and submitted to an inflammatory stimulus in the right hind paw (incision and suture). After 24 h the animals that presented hypernociception (at least 20% decrease in the baseline response to force - von Frey anesthesiometer) received a 0.1mL injection of one of mepivacaíne or control formulations at the side of the surgical wound. Local anesthesia was evaluated each 10 min with von Frey anesthesiometer. Data were submitted to Log-Rank, Tukey, Kruskal-Wallis and Student-Newman-Keuls tests (alpha=5%). Mepi-Epi provided higher success and duration of anesthesia (p<0.05) in the three studied models; no difference was observed between the liposomal formulations (p>0.05). No differences in the anesthesia onset were observed among formulations for IANB (p>0.05). It is concluded that the encapsulation in unilamelar and multilamelar liposomes was less effective than epinephrine to improve mepivacaine anesthetic efficacy in all studied models (AU)