Título:	Produção, caracterização e avaliação citotóxica de membranas lipídicas miméticas para a liberação do tripanocida N, N’-Squaramide 17 na linhagem CL-Brener de Trypanosoma cruzi
Autor(es):	Quijia Quezada, Christian Rafael
Orientador(es):	Carneiro, Marcella Lemos Brettas
Coorientador(es):	Bastos, Izabela Marques Dourado
Assunto:	Chagas, Doença de Lipossomas Efeito tripanocida Citotoxicidade Nanoestruturas Membrana lipídicas miméticas
Data de publicação:	13-Ago-2021
Data de defesa:	13-Nov-2018
Referência:	QUIJIA QUEZADA, Christian Rafael. Produção, caracterização e avaliação citotóxica de membranas lipídicas miméticas para a liberação do tripanocida N, N’-Squaramide 17 na linhagem CL-Brener de Trypanosoma cruzi. 2018. 82 f., il. Dissertação (Mestrado em Nanociência e Nanobiotecnologia)—Universidade de Brasília, Brasília, 2018.
Abstract:	Chagas disease affects about 25 million people in the world and is caused by Trypanosoma cruzi (T.c.). Currently, the only two drugs available for the its treatment - Benzonidazol (BZ) and nifurtimox - cause adverse effects in the patient. With this, new drugs have been studied in order to find more efficient therapeutic strategies, such as N, N'-Squaramide 17 (S), which represents a compound with excellent therapeutic potential. By means of nanotechnology, it is possible to improve the drug activity thanks to the properties of nanostructures that can promote sustained, release using low doses of drug and increasing its concentration in tissues. The objective of this work was to develop mimetic lipid membranes, from macrophage cell membrane lipids (lineage RAW 264.7) and encapsulate the S in this nanostructure, thus improving its trypanocidal efficacy on CL-Brener strain. Thus, nanostructures were developed and characterized: (1) mimetic lipid membrane containing S (MLS); (2) empty lipid mimetic membrane (MLV) and (3) N, N'- Squaramide 17 extruded (SE). Additionally, the physic-chemical characteristics and the cytotoxic and trypanocidal effects of these nanostructures were evaluated. The mean hydrodynamic diameter (dH) and zeta potential of the nanostructures were, respectively, 196.5 ± 11 nm / - 61.43 ± 2.3 mV for MLS; 203.1 ± 8.5 nm / - 12.9 ± 1.2 mV for MLV and 713.9 ± 112.6 nm / - 45.3 ± 7.45 mV for SE. It was observed that the MLS dH reduced around 70 nm after 10 days of storage, indicated possible release of S. The encapsulation of S in the mimetic membranes was verified using the analysis of vibrational spectroscopy in the infrared (IR) region and It was observed that the MLS nanostructure showed bands in 1788 cm-1 and 1674 cm-1 characteristics of the existing carbonyl groups in S. In relation to the cytotoxic effects, after 72h of treatment, it was observed that the MLV presented an excellent potential as vehicle for the delivery of drugs since there is no cytotoxicity in the mammalian cells under the concentrations tested. On the other hand, MLS, the nanostructure containing the S, was active against epimastigotes (IC50 of 15.9 ± 4.8 μM) and intracellular amastigotes (IC50 of 24.99 ± 4.8 μM), in addition, induced low cytotoxicity with IC50 of 626.7 ± 4.7 in VERO cells and 1974 ± 6 in RAW 264.7, From these data, the selectivity index (SI) was determined and it was observed that MLS induced trypanocidal activity superior to BZ in 57 times over epimastigota form and 9 times greater in amastigotas, showing a specific action. In the cell infection assays, the VERO cells were infected with trypomastigotes, incubated with half of the cytotoxicity IC50/2: (313 μM) of MLS for 12 h and then their trypanocidal activity was analyzed for eight days. It was observed on the 8th day, there was a greater inhibition in the infection rate of amastigotes (72%) than with the treatment with BZ (51%) (6.84 μM). In addition, the number of extracellular trypomastigotes was reduced by 81% after treatment with MLS while BZ reduced by 54%. MLS also induced structural changes in parasites such as fissures with a diameter of approximately 200 nm in the upper cellular part of the epimastigote and in tripomastigote showed a differentiation in amastigotes. In this way, MLS presented a promising trypanocidal efficacy. In addition, the fact that MLS has induced low cytotoxicity in mammalian cell lineages (RAW 264.7 and VERO) and high activity against the parasites demonstrates their specific toxicity, thus making this nanostructure promising for its application in the treatment of Chagas disease.
Unidade Acadêmica:	Instituto de Ciências Biológicas (IB) Departamento de Genética e Morfologia (IB GEM)
Informações adicionais:	Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Pós-Graduação em Nanociência e Nanobiotecnologia, 2018.
Programa de pós-graduação:	Programa de Pós-Graduação em Nanociência e Nanobiotecnologia
Licença:	A concessão da licença desta coleção refere-se ao termo de autorização impresso assinado pelo autor com as seguintes condições:Na qualidade de titular dos direitos de autor da publicação, autorizo a Universidade de Brasília e o IBICT a disponibilizar por meio dos sites www.bce.unb.br, www.ibict.br, http://hercules.vtls.com/cgi-bin/ndltd/chameleon?lng=pt&skin=ndltd sem ressarcimento dos direitos autorais, de acordo com a Lei nº 9610/98, o texto integral da obra disponibilizada, conforme permissões assinaladas, para fins de leitura, impressão e/ou download, a título de divulgação da produção científica brasileira, a partir desta data.
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