Effect of Dexamethasone-Loaded PLGA Nanoparticles on Oral Mucositis Induced by 5-Fluorouracil

Oral mucositis (OM) is characterized by the presence of severe ulcers in the oral region that affects patients treated with chemotherapy. It occurs in almost all patients who receive radiotherapy of the head and neck, as well as patients who undergo hematopoietic cell transplantation. The pathophysi...

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Main Authors: Susana Barbosa Ribeiro, Aurigena Antunes de Araújo, Maisie Mitchele Barbosa Oliveira, Alaine Maria dos Santos Silva, Arnóbio Antônio da Silva-Júnior, Gerlane Coelho Bernardo Guerra, Gerly Anne de Castro Brito, Renata Ferreira de Carvalho Leitão, Raimundo Fernandes de Araújo Júnior, Vinícius Barreto Garcia, Roseane Carvalho Vasconcelos, Caroline Addison Carvalho Xavier de Medeiros
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/13/1/53
Description
Summary:Oral mucositis (OM) is characterized by the presence of severe ulcers in the oral region that affects patients treated with chemotherapy. It occurs in almost all patients who receive radiotherapy of the head and neck, as well as patients who undergo hematopoietic cell transplantation. The pathophysiology of OM is complex, and there is no effective therapy. The aim of this study was to evaluate the effect of dexamethasone-loaded poly(<span style="font-variant: small-caps;">d</span>,<span style="font-variant: small-caps;">l</span>-Lactic-<i>co</i>-glycolic) nanoparticles (PLGA-DEX NPs) on an OM model induced in hamsters. The NPs were synthesized using the emulsification-solvent evaporation method and were characterized by the size, zeta potential, encapsulation efficiency, atomic force microscopy, physicochemical stability, and the in vitro release. The OM was induced by the administration of 5-FU on the first and second days and mechanical trauma on the 4th day of the experiment. PLGA-DEX NPs were administered to treat OM. The animals were euthanized on the 10th day. Macroscopic and histopathological analyses were performed, measurement of malonaldehyde (MDA) and ELISA was used to determine the levels of IL-1β and TNF-α. Immunoexpressions of NF-κB, COX-2, and TGF-β were determined by immunohistochemistry, and qRT-PCR was used to quantify the gene expression of the GILZ, MKP1, and NF-κB p65. The PLGA-DEX NPs (0.1 mg/kg) significantly reduced macroscopic and histopathological scores, decreased MDA, TNF-α and IL-1β levels, immunostaining for NF-κB, COX-2, TGF-β, and suppressed NF-κB p65 mRNA expression, but increased GILZ and MKP1 expression.
ISSN:1999-4923