Nanopartículas lipídicas sólidas contendo óleo essencial de Melaleuca alternifolia Cheel como plataforma inovadora no tratamento da candidíase orofaríngea

Abstract

Candida spp. species are commonly found in the oral microbiota residing as commensals; however, their status can change to pathogenic and cause oropharyngeal candidiasis, which can progress to candidemia. Despite the clinical and epidemiological importance of these infections, the therapeutic options are limited. This stimulates the search for new drugs, including those from natural sources, and technological strategies, such as nanotechnology. In this context, this study aimed to develop an innovative platform for the treatment of oropharyngeal candidiasis that comprises tea tree oil (TTO)-loaded solid lipid nanoparticles (SLN)–based hydrogel. The chemical composition of the oil was evaluated by gas chromatography coupled to mass spectrometry. The SLNs were characterized by the average hydrodynamic particle size (Z-average), polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (EE), morphology, stability, antioxidant potential, and in vitro cytotoxicity in a murine fibroblast cell line (L929). TTO-SLN were incorporated in hydrogel, and then the antifungal activity against standard yeasts such as C. albicans, C. glabrata, C. krusei, and C. guilliermondii was verified. Finally, ex vivo permeation of TTO from the hydrogel, using porcine buccal mucosa was analyzed. Thirteen constituents were identified in the TTO, whose percentage composition met the standards described by the ISO 4730: 2017. Regarding the TTO-SLN characterization, the respective values for Z-average, PdI, and ZP were 135.9 ± 6.65; 0.19 ± 0.04 and −31.07 ± 1.05, respectively. TTO-SLN showed an EE of 92.74% ± 0.012% and had a spherical shape. Additionally, the antioxidant activity ranged from 14.1% to 17.2%. TTO-SLN showed cytotoxic effect against L929 cell line (IC50 = 77.4 µg/mL). For at least 120 days, no significant changes were observed in the values of Z-average and PdI for TTO-SLN, and the TTO-loaded SLN-based hydrogel remained stable for at least 30 days, both under refrigeration. TTO-SLN and TTO-loaded SLNbased hydrogel exhibited fungicidal effect (minimum fungicidal concentration ranged between 5.60 and 11.20 mg/mL and between 5.53 and 11.06 mg/mL, respectively) and transmucosal permeation (70.52% ± 3.85%). It was concluded the TTO-loaded SLN-based hydrogel showed fungicidal effect outperforming the TTO as well as stability during the period of evaluation, and it was permeable through porcine cheek mucosa. The developed TTO-loaded SLN-based hydrogel can be a promising drug delivery system in oropharyngeal candidiasis.