Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia

Author(s)

Pedreira de Almeida, Ana Claudia ^{[1, 2]} ; Alves Pinto, Luciana Matos ^[2] ; Alves, Giuliana Piovesan ^{[3, 4]} ; de Morais Ribeiro, Ligia Nunes ^[1] ; Andrade Santana, Maria Helena ^[5] ; Saia Cereda, Cintia Maria ^[1] ; Fraceto, Leonardo Fernandes ^[6] ; de Paula, Eneida ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083862 Campinas, SP - Brazil

^[2] Fed Univ Alfenas UNIFAL, Fac Odontol, Alfenas - Brazil

^[3] Univ Fed Lavras, Dept Chem, Lavras - Brazil

^[4] Cristalia Prod Quim & Farmaceut Ltda, Itapira - Brazil

^[5] Univ Estadual Campinas, Fac Chem Engn, Dept Biotechnol Proc, Campinas, SP - Brazil

^[6] Sao Paulo State Univ Unesp, Inst Sci & Technol, Sorocaba - Brazil

• Document type: Journal article
• Source: Journal of Liposome Research; v. 29, n. 1, p. 66-72, 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants