Formulações nanoestruturas para uso como dessensibilizantes ao clareamento dentário de consultório: desenvolvimento, caracterização farmacológica, permeabilidade transdentária e citocompatibilidade

Abstract

Despite the efficacy of in-office tooth bleaching with hydrogen peroxide (H2O2), challenges such as inflammation and immediate mineral loss persist. This study aimed to develop nanostructured topical dental formulations for use as desensitizers in in-office tooth bleaching, characterize their pharmacological properties, and evaluate their transdental permeability and cytocompatibility. Nanoemulsions (NE) and gelled NE (NG) containing dexamethasone acetate (DEX), codeine phosphate (COD), and/or calcium phosphate (Ca3(PO4)2) for topical use were synthesized. The nanoemulsions (NE) were prepared using the phase inversion method, varying the surfactant concentration (SC) from 1 to 5%, and the most stable formulation was selected for physicochemical characterization over 45 days. We investigated the properties of droplet size, polydispersity index (PdI), zeta potential (ZP), pH, and rheology using Fourier Transform Infrared Spectroscopy, Transmission Electron Microscopy, and Ultraviolet-Visible Spectroscopy (UV-VIS). Cellular viability, apoptosis, necrosis, reactive oxygen species (ROS) levels, TRPA1 expression, and interleukins were assessed in NGs containing COD and COD + Ca3(PO4)2. Ex vivo permeability was tested using discs from bleached human third molars (H2O2, 3 applications of 15 minutes each). Data were analyzed descriptively (Origin Pro-8 software) and statistically (GraphPad Prism) by two-way ANOVA and Tukey´s post hoc test. Characterization revealed that the NEs contained 102% COD and 91% DEX, with an average droplet size of approximately 170 nm, PdI > 0.3, negative ZP, and a near-neutral pH. Immediate drug release levels were 4.62 ± 0.52 (COD) and 4.60 ± 1.93 (COD + Ca3(PO4)2). All formulations demonstrated cell viability. The formulations containing COD and/or Ca3(PO4)2 showed reduced apoptosis and necrosis, lower ROS production, decreased expression of TRPA1 and pro-inflammatory interleukins (IL-1ꞵ, IL-6), and increased levels of anti-inflammatory interleukins (IL-10) (p<0.0001). Therefore, the formulations exhibited appropriate pharmacological properties, enabled drug permeation through dental structures, and were cytocompatible.