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

Indexación ScopusAnesthetic 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. © 2020, The Author(s).https://www-nature-com.recursosbiblioteca.unab.cl/articles/s41598-020-76751-

A pre formulation study of tetracaine loaded in optimized nanostructured lipid carriers

Tetracaine TTC is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers NLC may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4 TTC. Structural properties and encapsulation efficiency EE amp; 8201; gt; amp; 8201;63 guided the selection of three pre formulations of different lipid composition, through a 23 factorial design of experiments DOE . DLS and TEM analyses revealed average sizes 193 220 nm , polydispersity lt; amp; 8201;0.2 , zeta potential amp; 8722; amp; 8201;21.8 to amp; 8722; amp; 8201;30.1 mV and spherical shape of the nanoparticles, while FTIR ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre formulation CP TRANS TTC showed phase separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid cetyl palmitate and liquid Transcutol lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach DOE and biophysical techniques two optimized pre formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic gt; amp; 8201;48 h and reducing TTC cytotoxicity against Balb c 3T3 cell

Injectable in situ forming nanogel: a hybrid Alginate-NLC formulation extends bupivacaine anesthetic effect

Finding an ideal anesthetic agent for postoperative pain control, with long action and low side effects, is still a challenge. Local anesthetics have potential for such application if their time of action is improved. This work introduces a new hybrid formulation formed by the association of a nanostructured lipid carrier with a biopolymeric system to encapsulate bupivacaine (BVC). The hybrid formulation was physicochemical and structurally characterized by DLS, TEM, DSC, XRD and FTIR-ATR, and it remained stable for 12 months at room temperature. In vivo analgesia and imaging tests showed that the hybrid system was able to modulate the release, and to increase the concentration of BVC at the site of action, by forming a nanogel in situ. Such nanogel improved over 5 times (>24 h) the anesthesia duration, when compared to free BVC at clinical (0.5%) doses. Therefore, this novel in situ-forming nanogel shows great potential to be used in postsurgical pain control, improving the action of BVC, without losing its versatility of (infiltrative) application10