LOCAL TOXICITY EVALUATION OF LIPOSOMAL LOCAL ANESTHETIC FORMULATIONS: PRILOCAINE AND MEPIVACAINE
Cíntia M. S. Cereda1; Giovana R. Tófoli2; Daniele R. Araujo1; Eneida de Paula1
1Departamento de Bioquímica, Instituto de Biologia - UNICAMP, Campinas, SP, Brasil;
2Departamento de Ciências Fisiológicas, Faculdade de Odontologia – UNICAMP, Piracicaba, SP, Brasil.
Prilocaine
(PLC) and mepivacaine (MVC) are aminoamide local anesthetics widely
used in regional anesthesia. We have previously reported the
preparation and characterization of 3% liposomal PLC (PLCLUV) and 2% liposomal MVC (MVCLUV)
formulations; both inducing enhanced analgesic effects when compared to
their aqueous solutions at equivalent concentrations (Cereda et al., J.
Pharm. Pharmac. Sci. 7:235, 2004; Araujo et al, Can. J. Anesth.51:566,
2004). In view of the fact that these formulations can be clinically
used in the future, we have decided to investigate their toxicity.
Firstly, the cell culture test was used to assess in vitro toxicity in our laboratory. In the present work, we report the in vivo local toxicity evaluation of these formulations using the paw-edema test. Male Wistar rats (250-350g, n= 6) were used in the groups: saline, Hepes buffer, liposomeslocal anesthetic-free, plain anesthetic solutions and
liposomal formulations, for each of the anesthetic studied: PLC or MVC.
Before the test, the animals were anesthetized with thiopental by
intraperitoneal route (40mg/kg). Later, the baseline volume of the
animal paw was measured and intraplantar injections (0.1 mL) of the
test solutions were given in the right paw. The paw volume measurement
was obtained with a plethysmometer (Ugo Basile) at 60, 120 and 180 min
after injection. PLCLUV and MVCLUV did
not evoke rat paw edema when compared to the control groups: saline,
Hepes buffer, PLC in solution, MVC in solution and Liposomeslocal anesthetic-free (p > 0.05). Our results led to the conclusion that the liposomal formulations studied (PLCLUV and MVCLUV) did not induce inflammatory effects on rat paw. Other in vivo
experiments are being conducted in our group to discard any kind of
toxic effect of these liposomal formulations, allowing for their
clinical use in the future. Supported by CAPES, CNPq and FAPESP.
|