Banca de DEFESA: LETÍCIA STRECK

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : LETÍCIA STRECK
DATA : 02/02/2017
HORA: 14:00
LOCAL: Sala de Aulas do PPgDITM
TÍTULO:

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PALAVRAS-CHAVES:

Benznidazole; lipid colloidal systems; citotoxicity in vitro; tripanocidal activity; nanotechnology;

PÁGINAS: 148
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Chagas disease is a kind of Neglected diseases, it represents a global health problem due to
the industry's lack of interest in research for new drugs. Benznidazole (BNZ), a drug available
in Brazil for the treatment of Chagas disease, and distributed by governement, presents some
limitations regarding its use, especially in the chronic's phase. Pharmaceutical technology
provides for the development of systems that increase drug solubility or increase its
concentration in infected cells / tissues which directly reflects the increased bioavailability
and therapeutic efficacy of BNZ. Thus, colloidal lipid systems (CLS), such as emulsions,
microemulsions and nanoemulsions, represent an interesting alternative for the increase of
oral and parenteral bioavailability of BNZ. This work aims to improve the method of
obtaining these systems and characterize the biocompatible CLS containing medium chain
triglycerides (Miglyol®812) stabilized by a suitable mixture of surfactants (soy
phosphatidylcholine and sodium oleate) associated with a co-solvent, besides evaluating the
trypanocidal effect of these systems. The improvement of the ideal conditions for obtaining
the systems of interest was evaluated by the study of the phase inversion temperature and the
addition of a new component, a co-solvent. The validation of the methodology followed the
guide recommended by ANVISA and "ICH". Liquid and translucent systems were formed
with addition of 2-methylpyrrolidone (NMP) as co-solvent with uniform droplet size and less
than 162.66 nm, when more than 5% of the surfactant mixture was added. The systems
remained stable for up to 60 days when stored at room temperature. When stored at 45 ° C,
the stability time was shorter, with a direct relationship with the co-solvent concentration, the
presence of BNZ and sialic acid Added. The rheology measurements showed a behavior
dependent on the amount of co-solvent added to the system. Polarized light microscopy and
low-angle X-ray scattering images confirmed the formation of isotropic systems when the
cosolvent is in a concentration greater than 5%. Atomic force microscopy images showed the
formation of large numbers of spherical, smooth droplets of a size well correlated with the
measurements obtained by the dynamic scattering of light. Addition of sialic acid to the
nanoemulsion containing 10% NMP did not increase drug uptake. The release of BNZ in
systems containing sialic acid at different concentrations was up to 3 (three) times faster than
systems without the substance. The mathematical model that fit all the systems investigated
was the Kormeyer-Peppas (r2 > 0.911), indicating mechanism non-Fickian of release. The
systems present biocompatibility in different cell lines (Vero, SiHa and LLC-MK2) over a
long period of exposure, up to 72 hours. The anti-epimastigote activity showed that much

smaller amounts of BNZ are able to inactivate this parasite life form when it is associated
with NMP-containing systems. The trypomastigote forms of the parasite showed greater
sensitivity to the constituents of the investigated systems and, cell death in concentrations up
to 170 times lower than when the drug was used alone and not incorporated in nanoemulsions.
Nanoemulsions have the ability to transport BNZ in biocompatible systems with excellent
trypanocidal activity, thus representing a promising future in the treatment of Chagas disease,
considering that to date there are no liquid dosage forms of administration which make it
impossible to adjust the dose, decrease the side effects.

MEMBROS DA BANCA:
Externo à Instituição - ANSELMO GOMES DE OLIVEIRA - UNESP
Externo ao Programa - 1218940 - ANTONIA CLAUDIA JACOME DA CAMARA
Presidente - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Interno - 1198847 - JOSE LUIS CARDOZO FONSECA
Externo à Instituição - VICTOR HUGO VITORINO SARMENTO - UFS