Medeiros, Caroline Addison Carvalho Xavier deRibeiro, Susana Barbosa2021-04-162021-04-162020-12-01RIBEIRO, Susana Barbosa. Efeito da dexametasona incorporada a nanopartículas poliméricas de poli (ácido lático-co-glicólico) (PLGA) na mucosite oral experimental. 2020. 101f. Tese (Doutorado em Biotecnologia) - Centro de Tecnologia, Universidade Federal do Rio Grande do Norte, Natal, 2020.https://repositorio.ufrn.br/handle/123456789/32254Oral mucositis (OM) is a frequent and limiting adverse reaction to cancer therapy, characterized by an intense inflammatory reaction and cumulative ulcer formation in the oral cavity. The aim of the present study was to evaluate the effect of dexamethasone (DEX) incorporated in polymeric nanoparticles (NP) of poly (lactic-co-glycolic acid) - PGLA - in the experimental model of oral mucositis induced by 5-fluorouracil (5-FU) in Golden syrian hamsters. The incorporation of DEX into the PLGA was performed using the solvent evaporation emulsification technique, followed by characterization with determination of the zeta potential, polydispersity index, particle size, atomic force microscopy, stability study, determination of encapsulation efficiency and study of in vitro release. To induce the OM model, 5-FU was administered intraperitoneally (i.p.) on the 1st (60mg/kg) and 2nd (40mg/kg) days of the experiment, followed by mechanical trauma on the oral mucosa performed on the 4th day, under effect anesthetic. The animals were distributed in the experimental groups: Normal, Mechanical Trauma, 5-FU, DEX (0,25; 0,5 or 1mg/kg) and NP PLGA-DEX (0,1; 0,5 or 1mg/kg). On the 11th day of the experimental model, the animals were euthanized. Macroscopic, histopathological analyzes, IL-1β and TNF-α quantification by ELISA, immunohistochemistry for MMP-2, COX-2, TGF-β and NF-κB p65, MIF, immunofluorescence for NF-κB markers were performed p65, SMAD 2/3 and p-SMAD 2/3, qRT-PCR assay to determine the gene expression of GILZ, MKP1, NF-κB p65 and AKT. Dexamethasone 1mg/kg and NP PLGADEX 0,1mg/kg demonstrated anti-inflammatory effects in the experimental OM model, with a significant reduction in macroscopic and histopathological scores (* p <0,05). Treatment with DEX or NP PLGA-DEX attenuated the levels of the pro-inflammatory cytokines TNF-α and IL-1β (* p <0,05), reduced the immunostaining for MMP-2, COX-2, TGF-β and NF-κB p65 (* p <0,05), suppressed the protein expression of MIF, NF-κB p65, SMAD 2/3 and p-SMAD 2/3 (* p <0,05), inhibited gene expression for NF-κB p65 and AKT, and increased the mRNA to GILZ and MKP1 (* p <0,05), compared to animals with untreated OM (group 5-FU). DEX 1mg/kg and the NP PLGA-DEX 0,1mg/kg formulation reduced inflammation in the 5-FUinduced oral mucositis model. The PLGA NP optimized the effect of DEX, since it was effective with a reduced dose of glucocorticoid.Acesso AbertoQuimioterapiaMucosite oralDexametasonaNanopartículas de PLGAVias de sinalizaçõesdoctoralThesis