EFAR - Escola de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/451
Notícias
O curso de Farmácia em Ouro Preto foi criado em 1839, sendo a mais antiga Escola de Farmácia da América Latina.
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6 resultados
Resultados da Pesquisa
Item Trypanocidal activity and increased solubility of benznidazole incorporated in PEG 4000 and its derivatives.(2021) Sousa, Lucas Resende Dutra; Azevedo, Maria Luíza Schaefer; Rocha, Dayana F.; Andrade, Ângela Leão; Amparo, Tatiane Roquete; Santos, Orlando David Henrique dos; Seibert, Janaína Brandão; Pereira, Luciano Rodrigues; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Barboza, Ana Paula Moreira; Neves, Bernardo Ruegger Almeida; Sales Junior, Policarpo Ademar Molina; Murta, Silvane Maria Fonseca; Novack, Kátia Monteiro; Santos, Viviane Martins Rebello dosSelecting a polymer depends on its characteristics, the properties of the drug and of the remaining ingredients in the formulation. The drug, when incorporated into a polymeric matrix, can show several advantages when compared with its conventional form. In this context, this work describes the preparation and characterization of polyethylene glycol (PEG 4000) and its derivative particles loaded with benznidazole, as well as evaluates their trypanocidal activity. In this work, reactions to modify the PEG 4000 polymer and the subsequent incorporation of the benznidazole were made. The nuclear magnetic resonance (NMR) analysis confirmed the efficiency in modifying the PEG chains. The morphology of polymeric films was observed by atomic force microscopy (AFM) and showed considerable changes on the film organization. The acetylation of PEG favored the stability of the system and an increase in the zeta potential from -14.83 to -25.54 mV was observed. Although encapsulation efficiency values between 30.14 and 39.48% were found, the enhanced benznidazole dissolution profile by microparticles enables the use of lower drug concentrations. This fact can be proven by the increased trypanocidal effect of benznidazole when encapsulated in BP3 microparticles. Finally, the high selectivity of the formulations for trypanocidal action guarantees their safety as an alternative for the treatment of the Chagas disease.Item Histopathological changes in the gastrointestinal tract and systemic alterations triggered by experimental oral infection with Trypanosoma cruzi.(2020) Carvalho, Lívia Mendes; Carvalho, Thaís Vieira de; Ferraz, Aline Tonhela; Marques, Flávia de Souza; Roatt, Bruno Mendes; Fonseca, Kátia da Silva; Reis, Levi Eduardo Soares; Carneiro, Cláudia Martins; Vieira, Paula Melo de AbreuChagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in almost all countries of Latin America. In Brazil, oral infection is becoming the most important mechanism of transmission of the disease in several regions of the country. The gastrointestinal tract is the gateway for the parasite through this route of infection, however, little is known about the involvement of these organs related to oral route. In this sense, the present study evaluated the impact of oral infection on the digestive tract in mice infected by Berenice-78 (Be-78) T. cruzi strain, in comparison with the intraperitoneal route of infection. In this work, the intraperitoneal route group showed a peak of parasitemia similar to the oral route group, however the mortality rate among the orally infected animals was higher when compared to intraperitoneal route. By analyzing the frequency of blood cell populations, differences were mainly observed in CD4+ T lymphocytes, and not in CD8+, presenting an earlier reduction in the number of CD4+ T cells, which persisted for a longer period, in the animals of the oral group when compared with the intraperitoneal group. Animals infected by oral route presented a higher tissue parasitism and inflammatory infiltrate in stomach, duodenum and colon on the 28th day after infection. Therefore, these data suggest that oral infection has a different profile of parasitological and immune responses compared to intraperitoneal route, being the oral route more virulent and with greater tissue parasitism in organs of the gastrointestinal tract evaluated during the acute phase.Item The effect of benznidazole dose among the efficacy outcome in the murine animal model. A quantitative integration of the literature.(2020) Molina, Israel; Melo, Luísa Helena Perin de; Aviles, Augusto Sao; Vieira, Paula Melo de Abreu; Fonseca, Kátia da Silva; Cunha, Lucas Maciel; Carneiro, Cláudia MartinsDespite more than 100 years since it was firstly described Chagas disease, only two drugs are available to treat Chagas disease: Nifurtimox launched by Bayer in 1965 and benznidazole launched by Roche in 1971. Drug discovery initiatives have been looking for new compounds as an alternative to these old drugs. Although new platforms have been used with the latest technologies, a critical step on that process still relies on the in vivo model. Unfortunately, to date, available animal models have limited predictive value and there is no standardization. With the aim to better understand the role of benznidazole, the current standard of care of Chagas disease, we performed this review. We intend to analyze the influence of the experimental design of the most used animal model, the murine model, in the assessment of the efficacy endpoint.Item Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi.(2019) Coelho, Gleicekelly Silva; Andrade, Josimara Souza; Xavier, Viviane Flores; Sales Júnior, Policarpo Ademar; Araújo, Bárbara Caroline Rodrigues de; Fonseca, Kátia da Silva; Caetano, Melissa Soares; Murta, Silvane Maria Fonseca; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Taylor, Jason GuyChagas disease is caused by infection with the parasite protozoan Trypanosoma cruzi and affects about 8 million people in 21 countries in Latin America. The main form of treatment of this disease is still based on the use of two drugs, benznidazole and nifurtimox, which both present low cure rates in the chronic phase and often have serious side-effects. Herein, we describe the synthesis of tricyclic coumarins that were obtained via NHC organocatalysis and evaluation of their trypanocidal activity. Molecular docking studies against trypanosomal enzyme triosephosphate isomerase (TIM) were carried out, as well as a theoretical study of the physicochemical parameters. The tricyclic coumarins were tested in vitro against the intracellular forms of Trypanosoma cruzi. Among the 18 compounds tested, 10 were more active than the reference drug benznidazole. The trypanocidal activity of the lead compound was rationalized by molecular docking study which suggested the strong interaction with the enzyme TIM by T. cruzi and therefore indicating a possible mode of action. Furthermore, the selectivity index of eight tricyclic coumarins with high anti-T. cruzi activity was above 50 and thus showing that these lead compounds are viable candidates for further in vivo assays.Item Pharmacokinetic and tissue distribution of benznidazole after oral administration in mice.(2017) Melo, Luísa Helena Perin de; Silva, Rodrigo Moreira da; Fonseca, Kátia da Silva; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; Reis, Levi Eduardo Soares; Molina, Israel; Oliveira, Rodrigo Corrêa de; Vieira, Paula Melo de Abreu; Carneiro, Cláudia MartinsSpecific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquidliquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 g/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 g/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, coulItem Different infective forms trigger distinct immune response in experimental Chagas disease.(2012) Vieira, Paula Melo de Abreu; Franscisco, Amanda Fortes; Machado, Evandro Marques de Menezes; Nogueira, Nívia Carolina; Fonseca, Kátia da Silva; Reis, Alexandre Barbosa; Carvalho, Andréa Teixeira de; Martins Filho, Olindo Assis; Tafuri, Washington Luiz; Carneiro, Cláudia MartinsAlthough metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-a and later of IFN-c by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-c, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease.