TY - JOUR
T1 - Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish
AU - Rodrigues da Silva, Gustavo H.
AU - Geronimo, Gabriela
AU - García-López, Juan P.
AU - Ribeiro, Lígia N.M.
AU - de Moura, Ludmilla D.
AU - Breitkreitz, Márcia C.
AU - Feijóo, Carmen G.
AU - de Paula, Eneida
N1 - Funding Information:
The authors thank FAPESP (G.H.R.S. Scholarship #17/15174-5, E.P. Grant #14/14457-5) and INCT-Bioanalítica (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.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85095936809&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-76751-6
DO - 10.1038/s41598-020-76751-6
M3 - Article
C2 - 33184457
AN - SCOPUS:85095936809
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 19733
ER -