Banca de DEFESA: ALINE DE SOUSA BARBOSA FREITAS PEREIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ALINE DE SOUSA BARBOSA FREITAS PEREIRA
DATE: 03/11/2022
TIME: 14:30
LOCAL: Online
TITLE:

Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats

KEY WORDS:

Periodontal disease. Hypoglycemics. Inflammation. Poly-lactic-co-glycolic acid. Availability.

PAGES: 114
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUBÁREA: Periodontia
SUMMARY:

There is a correlation between diabetes and periodontal disease, and Metformin (MET) in addition to controlling glycemic levels, has shown anti-inflammatory effects and decreased periodontal bone loss. When MET is delivered to a system of nanoparticles of biodegradable polymers, the advantage of increasing therapeutic efficacy can be presented. Objectives: This study consisted of evaluating the anti-inflammatory effects, bone loss and in vitro/in vivo availability of a polylactic-co-glycolic acid (PLGA) nanoparticle associated with MET in a ligature-induced periodontitis model. Materials and methods: The PLGA loaded with different doses of MET was characterized by its mean diameter, particle size, polydispensation index and trapping efficiency. Male Wistar rats were randomly divided into control and experimental groups with different doses of MET associated or not with PLGA, which received different treatments orally. Samples of maxilla and gingival tissue were used to evaluate bone loss and inflammation, by means of micro computed tomography (µCT), histopathological, immunohistochemistry, analysis of inflammatory cytokines and gene expression of proteins by quantitative RT-PCR. For the in vitro release assay (free of Met or PLGA + Met-12.5 mg/mL for 360 min), static Franz vertical diffusion cells were used. For analysis of availability, blood samples were collected at different time intervals, and analyzed by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results: The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm (p <0.05) with a polydispersity index of 0.285 (p <0.05), Z potential of 8.16 ± 1.1 mV (p < 0.01) and trapping efficiency (EE) of 66.7 ± 3.73. Treatment with MET 10 mg/kg + PLGA showed a low concentration of inflammatory cells, weak immunostaining for RANKL, cathepsin K, OPG and osteocalcin and decreased levels of IL-1β and TNF-α (p < 0.05), increase in AMPK gene expression (p <0.05) and decrease in NF-κB p65, HMGB1 and TAK-1 (p <0.05). PLGA + Met 10 mg/kg was released in the in vitro assay suggesting a kinetic model of parabolic diffusion with a release profile of 100% in 10 h by controlled diffusion. The in vivo assay showed the apparent volume of distribution Vz/F (PLGA + Met 10 mg/kg, 40971.8 mL/kg vs. Met 100 mg/kg, 2174.58 mL/kg) and the mean residence time MRTinf (PLGA + Met 10 mg/kg, 37.66 hr vs. Met 100 mg/kg, 3.34 hr). Conclusion: MET loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats. The formulation modifies pharmacokinetic parameters, such as apparent volume of distribution and mean residence time. PLGA + Met 10 mg/kg had a slower elimination rate compared to Met 100 mg/kg.

COMMITTEE MEMBERS:
Interna - 2374605 - AURIGENA ANTUNES DE ARAUJO
Interno - 1660087 - BRUNO CESAR DE VASCONCELOS GURGEL
Externo ao Programa - 3244198 - FRANCISCO LEONARDO DA SILVA JUNIOR - UFRNExterno à Instituição - JEAN NUNES DOS SANTOS - UFBA
Externo à Instituição - RAFAEL RODRIGUES LIMA - UFPA