Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice.
OBJECTIVE
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).


METHODS
BVC and MVC hydrochloride were encapsulated into LUV (0.4 micro m) composed of egg phosphatidylcholine, cholesterol and alpha-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 (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.


CONCLUSIONS
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 Araujo
Daniele R
DR
Department of Biochemistry, Institute of Biology, State University of Campinas, Sao Paulo, Brazil.
Cereda
Cíntia M S
CM
Brunetto
Giovana B
GB
Pinto
Luciana M A
LM
Santana
Maria Helena A
MH
de Paula
Eneida
E
D000698:Analgesia; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D008051:Lipid Bilayers; D008081:Liposomes; D008297:Male; D008619:Mepivacaine / Q000008:administration & dosage*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects; D009407:Nerve Block / Q000379:methods*; D009475:Neurons, Afferent / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D012584:Sciatic Nerve; D012995:Solubility
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D008051:Lipid Bilayers; D008081:Liposomes; D008619:Mepivacaine; D002045:Bupivacaine