Banca de DEFESA: HARLEY DA SILVA TAVARES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : HARLEY DA SILVA TAVARES
DATA : 27/07/2020
HORA: 09:00
LOCAL: UFSJ - CCO
TÍTULO:

Development of intraocular implantable polymeric systems for the treatment of toxoplasmosis 

PALAVRAS-CHAVES:

Spiramycin, Ocular toxoplasmosis, Toxoplasma gondii, Intraocular micro implant, Poly (D, L-lactic acid-glycolic acid) (PLGA).

PÁGINAS: 165
GRANDE ÁREA: Outra
ÁREA: Tecnologia e Inovação
RESUMO:

Ocular toxoplasmosis is a clinical presentation characterized by retinal / choroid inflammation and is the main cause of infectious posterior uveitis in the world. The aim of this work was to develop intraocular micro implants of poly (D, L-lactic acid-glycolic coacid) (PLGA) and spiramycin for the treatment of ocular toxoplasmosis. Solutions were prepared by dissolving between 8.33% to 25% (w/w) spiramycin and 75% to 91.67% (w/w) PLGA 50:50, PLGA 80:20 and PLGA85:15 in acetonitrile. After evaporation of acetonitrile, the powder mixture was molded at a temperature between 40 and 45 ° C. The micro implants were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimentry (TGA), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) Morphological Analysis. The method of quantifying spiramycin in micro-implants and vitreous humor by high performance liquid chromatography (HPLC) was previously developed and validated. The in vitro release study was performed in potassium phosphate buffer (PBS) pH 7.4 following sink conditions and ocular tolerance was evaluated by the chicken embryonic egg chorion-allantoid membrane test (HET-CAM). In vitro biocompatibility study was performed using human retinal pigment epithelium (ARPE-19) cells, and cytotoxicity was evaluated by Bromine 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H tetrazolate (MTT) reduction assay as well as cell cycle interference and migration of these cells. Cylindrical micro implants with mass between 2.85 and 3.15 mg, length between 2.78 mm and 3.22 mm and diameter between 0.85 mm and 0.95 mm were obtained. FTIR spectra demonstrated preservation of the typical absorption bands of PLGA and spiramycin after incorporation of this drug into the polymeric matrices. TGA and DSC thermograms evidenced the disappearance of the characteristic spiramycin peak after formulation development, due to the molecular dispersion of the drug within the polymeric matrix. Diffractograms analysis showed suggestive peaks of semicrystalline compounds, probably induced by heating. The morphological surface analysis of the micro implants obtained from PLGA 50:50 presented smooth and homogeneous. However, the surfaces of the micro implants obtained from PLGA 80:20 and 85:15 showed rough and heterogeneous, with the presence of pores or channels. The developed analytical method was validated to be linear, selective, precise and accurate. The drug was evenly distributed in the micro implants, with contents ranging from 97% to 103% of the labeled value. Through SEM analysis it was possible to verify the influence of pores or channels present in the polymeric matrix under the diffusion of spiramycin. Micro-implants promoted controlled release of spiramycin, with approximately 99% to 103% of the drug being releasedm by micro-implants composed of 50:50 PLGA on 56 consecutive days and PLGA 80:20 or PLGA 85:15 on 42 consecutive days. Micro implants were classified as non-irritant according to the HET-CAM, suggesting that these systems will be well tolerated after insertion into the vitreous cavity of the eye. The icro implants had low toxicity against ARPE-19 cells and did not promote disturbance in the process of migration of these cells or cell cycle modulation. Currently, in the pharmaceutical market there are no polymeric intraocular micro implants containing approved and available anti-toxoplasmosis drugs, which highlights these systems as an alternative for the treatment of ocular toxoplasmosis.

MEMBROS DA BANCA:
Presidente - 050.796.656-29 - GISELE RODRIGUES DA SILVA - UFOP
Externo ao Programa - 1150851 - RENE OLIVEIRA DO COUTO
Externo ao Programa - 1719911 - JULIANA TEIXEIRA DE MAGALHAES
Externo à Instituição - SANDRA APARECIDA DE LIMA MOURA - UFOP
Externo à Instituição - ANDRE LUIS MORAIS RUELA - UFOP