Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish

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.

Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

“…The first challenge to prepare a DTX formulation is imposed by its low aqueous solubility. Thus, considering our previous experience in the encapsulation of hydrophobic drugs [44][45][46] we decided to encapsulate DTX into NLC. For that, a 1% (w/w) NLC DTX formulation and its control (without drug, NLC CTRL ) were prepared.…”

Improved Local Anesthesia at Inflamed Tissue Using the Association of Articaine and Copaiba Oil in Avocado Butter Nanostructured Lipid Carriers

“…Table 2 also shows the encapsulation efficiency (%EE) of ATC by these particles, which was higher than 70% in both formulations, corresponding to a loading capacity > 8%. The spherical morphology of the particles was confirmed by transmission electron microscopy as well as their ability to prolong the in vitro release of ATC [8]. Of interest, the natural ATC-nanoparticles prepared with avocado butter (AB) and copaiba oil (CO) exhibited anti-inflammatory and analgesic activity over zebrafish larvae [8].…”

“…The spherical morphology of the particles was confirmed by transmission electron microscopy as well as their ability to prolong the in vitro release of ATC [8]. Of interest, the natural ATC-nanoparticles prepared with avocado butter (AB) and copaiba oil (CO) exhibited anti-inflammatory and analgesic activity over zebrafish larvae [8]. In this work, we evaluated structural and pharmacokinetic features of the NLC-ATC formulations, along with their effects in murine models of inflammatory pain, to demonstrate the pain control applicability of these plant-derived nanotherapeutics.…”

“…In a previous study [8], we described the preparation of different NLC formulations for the encapsulation of ATC using an experimental design (DoE) in which the selection of optimized formulations also considered their anti-inflammatory effects detected in a zebrafish model. Here, such optimized NLC formulations [8], classified by the type of their lipid excipients (natural and synthetic for comparison purposes), were employed. Their compositions (NLC-CO-A, NLC-A), and that of their controls prepared without ATC, are given in Table 1.…”

Isolation and characterization of plant-derived exosome-like nanoparticles from Carica papaya L. fruit and their potential as anti-inflammatory agent

“…Furthermore, zebrafish has demonstrated several advantages over other animal species and may serve as a substitute for rodents or provide supplementary information when used as a model for studying inflammatory diseases. Research shows that zebrafish possess an immune system similar to that of humans, making them a suitable model for such studies [ 26 – 28 ]. In addition, zebrafish have the advantage of low breeding costs, transparent embryos and larvae that allow the observation of specific cells, and permeability to small compounds [ 29 , 30 ].…”