Title: Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia
Author: Almeida, Ana Cláudia Pedreira De; Pinto, L. M. A.; Alves, G. P.; Ribeiro, L. N. M.; Santana, Maria Helena Andrade; Cereda, Cintia Maria Saia; Fraceto, Leonardo Fernandes; De Paula, E.
Is part of: JOURNAL OF LIPOSOME RESEARCH, v. 29, p. 66 - 72
Citation: Almeida, Ana Cláudia Pedreira De; Pinto, L. M. A.; Alves, G. P.; Ribeiro, L. N. M.; Santana, Maria Helena Andrade; Cereda, Cintia Maria Saia; Fraceto, Leonardo Fernandes; De Paula, E.; Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia. JOURNAL OF LIPOSOME RESEARCH, v.29, p. 66-72, 2019
Abstract: 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% (LUVLDC) was compared to LDC 2% solution without (LDCPLAIN) or with the vasoconstrictor epinephrine (1:100 000) (LDCVASO), in rat infraorbital nerve blockade model. The structural characterization revealed liposomes with spherical shape, average size distribution of 250nm and low polydispersity even after LDC incorporation. Zeta potential laid around -30mV and the number of suspended liposomal particles was in the range of 10(12) 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 LDCPLAIN (p<0.05). Also, the liposomal formulation prolonged the sensorial nervous blockade duration (approximate to 70min), in comparison with LDCPLAIN (45min), but less than LDCVASO (130min). 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.
Keywords: drug delivery; lidocaine; liposomes;
Subjects: CIENCIAS_BIOLOGICAS; Farmacologia Bioquímica e Molecular;
Funding: Financial support from Sao Paulo Science Foundation - FAPESP [2014/14457-5] and Coordenacao de Aperfeicoamento de pessoal de Nivel Superior (PICDT/CAPES Program) are acknowledged.