Promising potential of articaine-loaded poly(epsilon-caprolactone) nanocapules for intraoral topical anesthesia

Abstract

To determine whether the permeation capacity and analgesic efficacy of articaine (ATC) could be increased and cytotoxicity decreased by encapsulation in poly(ɛ-caprolactone) nanocapsules (ATCnano), aiming at local or topical anesthesia in dentistry. Cellular viability was evaluated (using the MTT test and fluorescence microscopy) after 1 h and 24 h exposure of HaCaT cells to ATC, ATCnano, ATC with epinephrine (ATCepi), and ATC in nanocapsules with epinephrine (ATCnanoepi). The profiles of permeation of 2% ATC and 2% ATCnano across swine esophageal epithelium were determined using Franz-type vertical diffusion cells. Analgesic efficacy was evaluated with a von Frey anesthesiometer in a postoperative pain model in rats, comparing the 2% ATC, 2% ATCnano, 2% ATCepi, and 2% ATCnanoepi formulations to 4% ATCepi (a commercially available formulation). We show that use of the nanocapsules decreased the toxicity of articaine (P<0.0001) and increased its flux (P = 0.0007). The 2% ATCepi and 4% ATCepi formulations provided higher analgesia success and duration (P<0.05), compared to 2% ATC, 2% ATCnano, and 2% ATCnanoepi. Articaine-loaded poly(ɛ-caprolactone) nanocapsules constitute a promising formulation for intraoral topical anesthesia (prior to local anesthetic injection), although it is not effective when injected in inflamed tissues for pain control, such as irreversible pulpitis.

Polymeric Nanocapsules Loaded with Lidocaine: A Promising Formulation for Topical Dental Anesthesia

“…The analysis of pH also contributes to understanding nanoparticle stability. The decrease in pH could be linked to the hydrolysis of poly(epsilon-caprolactone) nanocapsules, resulting in an increase in the concentration of terminal carboxylic groups due to the relaxation of polymeric chains, as documented in previous studies [8,10,16]. In our investigation, a slight pH reduction was noted in the initial observation period, followed by stability over the subsequent two periods (60 and 120 days), consistent with previous findings [8].…”

“…Substantial alterations in these parameters signal the formation of aggregates and a decrease in stability [16]. The diameter of LDC-Nano was consistent with the dimensions reported in the literature for polymeric nanocapsules loaded with lidocaine [8] and articaine encapsulated in poly(epsilon-caprolactone) nanocapsules [10,17]. In fact, minor fluctuations were noted in the diameter sizes of various polymeric nanoparticles [7,8,[18][19][20].…”

“…The samples subjected to analysis included poly(epsilon-caprolactone) nanocapsules (Nano), lidocaine encapsulated in poly(epsilon-caprolactone) nanocapsules (LDC-Nano), poly(epsiloncaprolactone) (PCL), a physical mixture of lidocaine and poly(epsilon-caprolactone) (PM LDC + PCL), and lidocaine (LDC). HaCaT cells were cultured similarly to a previous method employed by our group [9,10]. Dulbecco's Modified Eagle Medium (DMEM) supplemented with 100 U/mL penicillin, 10% fetal bovine serum, and 100 µg/mL streptomycin (Vitrocell, Campinas, Brazil) were used.…”

Present status and future directions—Mechanisms and management of local anaesthetic failures

“…Variables such as the time between topical anaesthetic application and the injection, the site of injection and the type as well as the concentration of the topical anaesthetic agents are all factors that may influence the efficacy of topical anaesthesia (Drum et al, 2011; Fukayama et al, 2002; Meechan John, 2008; Nakanishi et al, 1996; Nusstein & Beck, 2003). In future, new forms of topical anaesthesia with higher permeation may be achievable (Batista da Silva et al, 2021).…”

“…There are concerns regarding possible adverse effects of articaine and prilocaine versus lidocaine when used as anaesthetic solutions in dentistry (Batista da Silva et al, 2021; Becker & Reed, 2012; Sambrook & Goss, 2011). In contrast to these reports, two systematic reviews and meta‐analyses did not show a significant difference in adverse effects between 2% lidocaine and 4% articaine (Katyal et al, 2010; Su et al, 2016).…”