Banca de DEFESA: THAYSE SILVA MEDEIROS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : THAYSE SILVA MEDEIROS
DATE: 25/07/2024
TIME: 09:00
LOCAL: Videoconferência
TITLE:

NANOPARTÍCULAS HÍBRIDAS LIPÍDICAS-POLIMÉRICAS CATIÔNICAS CARREGADAS COM BENZNIDAZOL PARA TRATAMENTO DA INFECÇÃO POR Trypanosoma cruzi

KEY WORDS:

Trypanosoma cruzi; Benznidazole; Nanotechnology;

PAGES: 124
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Chagas disease, also known as American Trypanosomiasis, is a neglected tropical illness
caused by the hemoflagellate protozoan Trypanosoma cruzi. Currently, only two drugs,
Benznidazole (BNZ) and Nifurtimox, has been approved for disease treatment, with BNZ
being the only one authorised for use in Brazil. However, BNZ faces various limitations
including low bioavailability and higher toxicity to the host. Parasite resistance to the
treatment has been also reported. In this regard, nanotechnological formulations for drug
delivery have emerged as a promising alternative to improve the pharmacological
properties and bioavailability of this drug. In this study, we have investigated the in vitro
effectiveness of cationic PLGA-cholesterol hybrid loaded with BNZ as a drug-delivery
platform against T. cruzi. The nanoprecipitation method was used to obtain the HNPs,
and their size, polydispersity index, and zeta potential were determined. Following PEI
functionalization, the size of the NPHs was less than 200 nm, with homogeneous particle
distribution and a zeta potential ranging from -20 to +10. The efficiency of encapsulation
was determined to be 40% for anionic HNPs, increasing to 54% for cationic counterparts.
FTIR and XRD analyses corroborated the successful encapsulation of BNZ.
Morphological characterization throughout scanning electron microscopy (SEM)
demonstrated spherical-shaped particles, regardless of their composition. In vitro studies
showed that nanoparticles are safe at the evaluated concentrations for cardiomyoblasts.
Furthermore, compared to the free drugs, HNPs exhibited higher trypanocidal effects
against intracellular amastigotes, as evidenced by IC50 values of <5.9 and 38.6,
respectively. However, no statistical difference was observed between the trypanocidal
activity of the anionic and cationic systems. Fluorescence microscopy images showed the
internalization of HNPs from 5 minutes onward. Taken together, our results showed the
successful development of HNPs, underscoring their potential as a promising platform
for the delivery of therapeutic agents used in the treatment of Trypanosoma cruzi
infection.

COMMITTEE MEMBERS:
Externo à Instituição - GABRIEL LIMA BARROS DE ARAUJO - USP
Presidente - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Externo à Instituição - ELTON MARLON DE ARAUJO LIMA - UFPE
Interno - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA
Externo à Instituição - ROBERTO NICOLETE - FIOCRUZ