Article

Download article 		Title: Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish
Author: Rodrigues Da Silva, Gustavo H.; Geronimo, Gabriela; García-lópez, Juan P.; Ribeiro, Lígia N. M.; De Moura, Ludmilla D.; Breitkreitz, Márcia C.; Feijóo, Carmen G.; De Paula, Eneida
Year: 2020
Is part of: Scientific Reports, v. 10, p. 19733 -
DOI: https://doi.org/10.1038/s41598-020-76751-6

Citation: Rodrigues Da Silva, Gustavo H.; Geronimo, Gabriela; García-lópez, Juan P.; Ribeiro, Lígia N. M.; De Moura, Ludmilla D.; Breitkreitz, Márcia C.; Feijóo, Carmen G.; De Paula, Eneida; Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish. Scientific Reports, v.10, p. 19733-, 2020

Abstract: Anesthetic failure is common in dental inflammation processes, even when modern agents, such as articaine, are used. Nanostructured lipid carriers (NLC) are systems with the potential to improve anesthetic efficacy, in which active excipients can provide desirable properties, such as anti-inflammatory. Coupling factorial design (FD) for in vitro formulation development with in vivo zebrafish tests, six different NLC formulations, composed of synthetic (cetyl palmitate/triglycerides) or natural (avocado butter/olive oil/copaiba oil) lipids were evaluated for loading articaine. The formulations selected by FD were physicochemically characterized, tested for shelf stability and in vitro release kinetics and had their in vivo effect (anti-inflammatory and anesthetic effect) screened in zebrafish. The optimized NLC formulation composed of avocado butter, copaiba oil, Tween 80 and 2% articaine showed adequate physicochemical properties (size=217.7 +/- 0.8 nm, PDI=0.174 +/- 0.004, zeta potential=- 40.2 +/- 1.1 mV, %EE=70.6 +/- 1.8) and exhibited anti-inflammatory activity. The anesthetic effect on touch reaction and heart rate of zebrafish was improved to 100 and 60%, respectively, in comparison to free articaine. The combined FD/zebrafish approach was very effective to reveal the best articaine-in-NLC formulation, aiming the control of pain at inflamed tissues.

Keywords: articaine; drug delivery systems; local anesthetics; nanostructured lipid carriers; zebrafish;
Subjects: CIENCIAS_BIOLOGICAS; Farmacologia Bioquímica e Molecular; CIENCIAS_BIOLOGICAS; Biofísica; Biofísica de Processos e Sistemas;

Funding: The authors thank FAPESP (G.H.R.S. Scholarship #17/15174-5, E.P. Grant #14/14457-5) and INCT-Bioanalitica (M.C.B.) for research Grant. FAPESP provided the financial support for G.H.R.S during his internship in Andres Bello University-Chile. E.P. was supported by CNPq /Brazil (E.P. fellowship), C.G.F. by FONDECYT 1171199 and J.P.G. by CONICYT Scholarship 21151452. We also acknowledge DFL Ind. Com. S.A. for kindly supplying articaine. 		Financed by: