Banca de DEFESA: ALAINE MARIA DOS SANTOS SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : ALAINE MARIA DOS SANTOS SILVA
DATA : 27/06/2019
HORA: 14:00
LOCAL: SALA 2 DO PPGCF
TÍTULO:

Fluorescent labeled benznidazole-loading biodegradable nanoparticles
to improve drug targeting in infected cells with parasites

PALAVRAS-CHAVES:

Benznidazole. Efficacy in vivo. Polymeric nanoparticles. Fluorescent probe. Trypanosoma cruzi.

PÁGINAS: 153
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Benznidazole (BNZ) is the drug of choice for the treatment of patients with infection by Trypanosoma cruzi. Despite its wide use, it presents problems of efficacy due to the high toxicity, difficulty to cross the biological barriers, besides its low solubility in aqueous medium. Nanoparticles have the proven ability to cross biological barriers and intracellular drug targeting, especially when surface ligants are conjugated to increase drug targeting for infected cells. The aim of the present work is to develop functionalized and fluorescent nanoparticles of poly (lactide-co-glycolide) (PLGA) for modified release of benznidazole. The particles were produced by the emulsification-solvent evaporation method. The standardization of the formulation and the parameters of the preparation were monitored by measurements of average particle size, polydispersity index, zeta potential, atomic force microscopy (AFM), scanning electron microscopy (SEM), confocal microscopy (CM), attenuated total reflectance fourier transforms infrared spectroscopy (ATR–FTIR), thermogravimetric analysis (TGA), encapsulation efficiency and in vitro studies. Stable and spherical polymeric nanoparticles below 300 nm were optimized, with encapsulation efficiency greater than 95%. In vitro release kinetics of the drug demonstrated slow release of the nanoparticles and improved biological activity of nanoparticles containing BNZ. In vitro assays in normal cells (Hek 293), tumor cells (Hep G2 and HT-29), amastigotes (H9c2 and Dm28c strains) and with epimastigotes (Y, CL-Brenner and Dm28c strains) showed an increase in the potency of the nanoparticles on the free BNZ. The analysis by confocal microscopy showed that nanoparticles enter the parasite with high efficiency, especially those functionalized with sialic acid and cholesterol. In vivo tests revealed that nanoparticles containing BNZ had similar effect to free BNZ, even when used in a concentration 20 times lower. Thus, the present work systematically addresses the development of a nanotechnological system with innovative potential for increasing the efficacy of benznidazole in cells infected with Trypanosoma cruzi.

MEMBROS DA BANCA:
Presidente - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Externo à Instituição - BOLIVAR PONCIANO GOULART DE LIMA DAMASCENO - UEPB
Externo à Instituição - CARLOS ALBERTO ROBELLO PORTO - IP
Externo à Instituição - JOSÉ LAMARTINE SOARES SOBRINHO - UFPE
Interno - 2275890 - MARCELO DE SOUSA DA SILVA
Interno - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA