Modulação da captação de nanoemulsão lipídica no sistema fagocitário mononuclear hepático pela ação da cloroquina

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Pós-Graduação em Nanociência e Nanobiotecnologia, 2020.A aplicação da nanotecnologia na terapia do câncer tem sido promissora. Por ser uma tecnologia que fornece uma abordagem abrangente e única contra o câncer por meio do diagnóstico, prevenção, terapia e medicina personalizada. Com essa tecnologia, podem ser utilizadas diferentes estratégias para o tratamento do câncer como, por exemplo, o medicamento terapêutico sendo carreado por nanopartículas e com alvo específico, liberação controlada do agente terapêutico na região de interesse e métodos para o diagnóstico precoce. Embora nanopartículas geralmente se acumulem 10 vezes mais em tumores quando comparado com fármacos convencionais, menos de 1% da dose injetada atinge tipicamente o tumor, pois ficam retidas no fígado e baço. Os macrófagos específicos para o fígado, chamados de células de Kupffer e que constituem uma das principais barreiras no uso de nanopartículas para o tratamento do câncer, foram identificados pela primeira vez no fígado por von Kupffer e correspondem a maior população de macrófagos teciduais. Essas Células de Kupffer fazem parte do Sistema Fagocitário Mononuclear e são predominantemente distribuídas no lúmen dos sinusóides hepáticos, exibindo atividade endocítica contra os materiais que passam pelo sangue e entram no fígado. Por esse motivo, as células de Kupffer são centrais no processo de eliminação de nanopartículas que atravessam as barreiras epiteliais do corpo. Diante da problemática apresentada, este trabalho teve por objetivo modular a captação de uma nanoemulsão lipídica no sistema fagocitário mononuclear hepático pela ação da cloroquina para bloquear temporariamente a endocitose das nanopartículas pelas células de Kupffer.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Fundação de Apoio à Pesquisa do Distrito Federal (FAP/DF); Conselho Nacional de Desenvolvimento Científico e Tecnológico e Institutos Nacionais de Ciência e Tecnologia (INCTs).The application of nanotechnology in cancer therapy has been promising. It is a technology that provides a comprehensive and unique approach to cancer through diagnosis, prevention, therapy and personalized medicine. Different strategies for the treatment of cancer can be used, for example, the therapeutic drug being carried by nanoparticles and with a specific target, controlled release of the therapeutic agent in the region of interest and methods for early diagnosis. Although nanopharmaceuticals generally accumulate 10 times more in tumors when compared to conventional drugs, less than 1% of the injected dose typically reaches the tumor, because they get stuck in the liver and spleen. The liver-specific macrophages called Kupffer cells are one of the main barriers in the use of nanoparticles for the treatment of cancer. They were first identified in the liver by von Kupffer and correspond to the largest population of tissue macrophages. Kupffer cells are part of the Mononuclear Phagocyte System and are predominantly distributed in the lumen of hepatic sinusoids exhibiting endocytic activity against materials that pass through the blood and enter the liver. For this reason, Kupffer cells are central to the process of eliminating nanoparticles that cross the body's epithelial barriers. In view of the problem presented, this study aimed to modulate the capture of a lipid nanoemulsion in the hepatic mononuclear hepatic phagocytic system by the action of chloroquine to temporarily block an endocytosis of the nanoparticles by Kupffer cells

Nano vacunas COVID-19 : las primeras vacunas de nanopartículas lipídicas de ARN siendo aprobadas en la historia : revisión

Um novo coronavírus, identificado em Wuhan, China, se espalhou globalmente, infectando milhões de pessoas e causando morbidade e mortalidade significativas. O estado de pandemia, declarado pela Organização Mundial da Saúde em 11 de março de 2020, transformou o mundo e fez com que as pessoas se adaptassem ao distanciamento social para controlar a disseminação do vírus. A corrida contra o tempo em busca de soluções terapêuticas tornou-se imprescindível, e a nanotecnologia pode conseguir disponibilizar vacinas em tempo recorde para estimular a imunização dos indivíduos. Desde o início de 2020, os cientistas e empresas estão avançando rapidamente para disponibilizar vacinas candidatas num ritmo diferenciado comparado a outras pandemias que existiram. Esta revisão apresenta, brevemente, os prós e contras das vacinas de terceira geração, Moderna / NIAID e Pfizer - BioNTech, que estão em testes de fase 3, com base em nanopartículas de RNA lipídico. Grandes esforços colaborativos estão sendo investidos para que em breve a população mundial receba doses de vacinas com eficácia comprovada e possibilite o aumento da sobrevida, visto que a pandemia já ocasionou muitas perdas irreversíveis.A new coronavirus, identified in Wuhan, China, has spread globally, infecting millions of people and causing significant morbidity and mortality. The pandemic state, declared by the World Health Organization on March 11, 2020, transformed the world and made people adapt to social distance to control the spread of the virus. The race against time in search of therapeutic solutions has become essential, and nanotechnology may be able to make vaccines available in record time to stimulate the immunization of individuals. Since the beginning of 2020, scientists and companies are rapidly advancing to make vaccine candidates available at a different rate compared to other pandemics that have existed. This review briefly presents the pros and cons of the third generation vaccines, Moderna / NIAID and Pfizer - BioNTech, which are in phase 3 tests, based on lipid RNA nanoparticles. Great collaborative efforts are being invested so that soon the world population will receive doses of vaccines with proven efficacy and enable increased survival, since the pandemic has already caused many irreversible losses.Un nuevo coronavirus, identificado en Wuhan, China, se ha propagado a nivel mundial, infectando a millones de personas y provocando una morbilidad y mortalidad significativas. El estado pandémico, declarado por la Organización Mundial de la Salud el 11 de marzo de 2020, transformó el mundo e hizo que las personas se adaptaran a la distancia social para controlar la propagación del virus. La carrera contrarreloj en busca de soluciones terapéuticas se ha vuelto fundamental, y la nanotecnología puede hacer que las vacunas estén disponibles en un tiempo récord para estimular la inmunización de los individuos. Desde principios de 2020, los científicos y las empresas están avanzando rápidamente para que los candidatos a vacunas estén disponibles a un ritmo diferente en comparación con otras pandemias que han existido. Esta revisión presenta brevemente los pros y los contras de las vacunas de tercera generación, Moderna / NIAID y Pfizer - BioNTech, que se encuentran en pruebas de fase 3, basadas en nanopartículas de ARN lipídico. Se están invirtiendo grandes esfuerzos de colaboración para que pronto la población mundial reciba dosis de vacunas de probada eficacia y permitan una mayor supervivencia, ya que la pandemia ya ha provocado muchas pérdidas irreversibles

Hydroxychloroquine in fighting COVID-19 : What led WHO to suspend clinical trial of drug?

Purpose: On March 11, 2020 the pandemic status of COVID-19 (Coronavirus Disease 2019) was declared. The milestone of thousands of daily deaths from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reached worldwide. So far, there is still no proven effective treatment against this disease. This study summarizes the main clinical findings on the use of hydroxychloroquine (HCQ) to treat COVID-19. The goal is to gather the evidence that led WHO to suspend the HCQ arm of its Solidarity Trial, contributing to the understanding of its denouement. Methods: LitCovid platform was searched for the term "hydroxychloroquine” in the “treatment” field. All clinical studies published in the period from January 1st to June 17th were included in the review. Results: We included ten articles on HCQ in COVID-19 positive patients (eight non-randomized and two randomized clinical studies). Most studies did not report a benefit in the use of HCQ. There is no evidence of decreased risk of intubation or death, and in some cases adverse effects have been reported, such as abnormal liver function, transient blurred vision, diarrhea. Conclusions: The overview of the available data on HCQ in COVID-19 patients can guide future studies, still needed to support public policies and health authorities in fighting COVID-19

Global perspective of studies with hydroxychloroquine for the treatment of COVID-19

Objetivo: analisar os recentes estudos com a hidroxicloroquina no tratamento da COVID-19. Métodos: comunicação breve relatando os principais resultados com o uso da hidroxicloroquina em ensaios clínicos e o panorama mundial desses estudos. Resultados: a maioria dos ensaios clínicos no mundo é com a hidroxicloroquina, e os resultados com o seu uso são variados. Conclusão: é urgente avaliar melhor a eficácia da hidroxicloroquina no possível tratamento da COVID-19 em pacientes não severos.Objective: analyze the most recent studies with hydroxychloroquine in the treatment of COVID-19. Methods: brief communication reporting the main results with the use of hydroxychloroquine in clinical trials and the global panorama of these studies. Results: the majority of clinical trials in the world are with hydroxychloroquine, and the results with its use are varied. Conclusion: it is urgent to better evaluate the efficacy of hydroxychloroquine in the possible treatment of COVID-19 in non-severe patients

COVID-19 : ¿Se integran las vacunas de ADN / ARN en el genoma?

A nova pandemia de coronavírus trouxe a necessidade de pesquisadores trabalharem incansavelmente na busca por terapias ou vacinas que permitissem controlar a disseminação do vírus pelo mundo. Felizmente, existem duas vacinas de RNA contra COVID-19 que concluíram os testes clínicos e foram aprovadas em alguns países. São as primeiras vacinas de terceira geração aprovadas na história e em registro de tempo. Mas,ainda temosalgumas preocupações sobre a segurança das vacinas de DNA / RNA. Trazemos aqui uma discussão sobre a segurança do DNA / RNA: essas vacinas podem ser integradas ao genoma? Na verdade, as vacinas de DNA têm uma chance infinita de se integrar ao genoma da célula, mas essa chance infinita é igual a zero quando usadas com vacinas baseadas em RNA. As vacinas à base de ácido nucléico (DNA e RNA) têm se correspondido em vantagens, tornando-se alternativas promissoras para garantir a imunização do novo coronavírus.The new coronavirus pandemic brought the need for researchers to work tirelessly in the search for therapies or vaccines that would allow control of the spread of the virus around the world. Fortunately there are two RNA vaccines against COVID-19 that have finished clinical tests and are approved in some countries. They are the first third generation vaccines approved in history and in time record. But still have some concerns about safety of DNA/RNA vaccines. Here we bring a discussion about safety of DNA/RNA: can these vaccines be integrated to the genome? In fact, DNA vaccines have an infinite chance to integrate in the cell's genome, but this infinite chance is equal zero when used with RNA-based vaccines. The vaccines based on nucleic acid (DNA and RNA) have been corresponding in advantages, becoming promising alternatives to guarantee the immunization of the new coronavirus.La nueva pandemia de coronavirus trajo la necesidadde que los investigadores trabajaran incansablemente en la búsqueda de terapias o vacunas que permitieran controlar la propagación del virus por todo el mundo. Afortunadamente, existen dos vacunas de ARN contra COVID-19 que han finalizado las pruebas clínicas y están aprobadas en algunos países. Son las primeras vacunas de tercera generación aprobadas en la historia y en el tiempo récord. Pero, todavía tenemosalgunas preocupaciones sobre la seguridad de las vacunas de ADN / ARN. Aquí traemos una discusiónsobre la seguridad del ADN / ARN: ¿se pueden integrar estas vacunas al genoma? De hecho, las vacunas de ADN tienen una posibilidad infinita de integrarse en el genoma de la célula, pero esta posibilidad infinita es igual a cero cuando se usa con vacunas basadas en ARN. Las vacunas basadas en ácido nucleico (ADN y ARN) se han correspondido en ventajas, convirtiéndose en alternativas prometedoras para garantizar la inmunización del nuevo coronavirus

The landscape of nanotechnology strategies against Covid-19 : products and diagnostics, vaccines and treatments

The pandemic state, declared by the World Health Organization, on March 11, 2020, has tested society's adaptability and response. A race against time to seek strategies to fight the disease of the new coronavirus contributes to the union of scientists from all over the world, including using nanotechnology Thus, the objective of the study was described the landscape of nanotechnology strategies against COVID-19,highlighting mainly the products and diagnostics, vaccines and treatments that are or can be used. A literature review was carried out in studies published from February to November2020 in PubMed, Scielo, and Google Scholar databases. According to the indexes of the various databases, search terms were used: “new coronavirus 2019”, “COVID-19”, “severe acute respiratory syndrome” Nanotechnology against COVID-19”, “COVID-19 Vaccines” without any language restrictions. The use of nano-based materials has indicated a great potential against dissemination of COVID-19, with the production of products, diagnostics, vaccines and treatments. Our results demonstrate that nanotechnology offers processes, materials and tools that contribute to increase the sensitivity, agility and reliability of the diagnostic, in addition to providing more effective options for prevention, diagnostic and therapies

One year after the WHO alert for COVID-19: what is next? / Um ano após o alerta da OMS para COVID-19: o que vem a seguir?

In December 2019, an outbreak of atypical pneumonia was discovered, later revealed to be due to a new virus identified as SARS-CoV-2, responsible for causing the coronavirus disease (COVID-19). The purpose is brings the main changes and discoveries, after a year that PHEIC was declared. We argue that after one year since PHEIC was declared, a lot has changed since then, in this sense, carried out a bibliographic review. We conducted a survey of articles published in the PUBMED and Google Scholar databases, from January 2020 to January 2021, which released data from studies related to transmission, treatment, vaccines, new variants for COVID-19. After the novel virus spread to other countries and caused hundreds of deaths, the World Health Organization issued its alarm on January 30, 2020, known as PHEIC. After a year that the alarm was given a lot has changed. The first major change was the beginning of a COVID-19 pandemic on March 11, 2020. Many discoveries were made, from a better understanding of transmission, treatment, vaccines and challenges with new strains that arose after selective pressure. 

Um ano após o alerta da OMS para Covid-19 : o que vem a seguir?

Introdução: Em dezembro de 2019, foi descoberto um surto de pneumonia atípica, posteriormente, revelado ser devido a um novo vírus identificado como SARS-CoV-2, responsável por causar a doença coronavírus (COVID-19). O objetivo se baseou em trazer as principais mudanças e descobertas, após um ano que o PHEIC foi declarado. Argumentamos que após um ano desde que o PHEIC foi declarado, muita coisa mudou desde então, nesse sentido, realizou-se uma revisão bibliográfica. Depois que o novo vírus se espalhou para outros países e causou centenas de mortes, a Organização Mundial da Saúde emitiu seu alarme em 30 de janeiro de 2020, conhecido como PHEIC. Depois de um ano que o alarme foi dado, muita coisa mudou. A primeira grande mudança foi o início de uma pandemia de COVID-19 em 11 de março de 2020. Muitas descobertas foram feitas, a partir de um melhor entendimento da transmissão, tratamento, vacinas e desafios com novas cepas que surgiram após pressão seletiva.In December 2019, an outbreak of atypical pneumonia was discovered, later revealed to be due to a new virus identified as SARS-CoV-2, responsible for causing the coronavirus disease (COVID-19). The purpose is brings the main changes and discoveries, after a year that PHEIC was declared. We argue that after one year since PHEIC was declared, a lot has changed since then, in this sense, carried out a bibliographic review. We conducted a survey of articles published in the PUBMED and Google Scholar databases, from January 2020 to January 2021, which released data from studies related to transmission, treatment, vaccines, new variants for COVID-19. After the novel virus spread to other countries and caused hundreds of deaths, the World Health Organization issued its alarm on January 30, 2020, known as PHEIC. After a year that the alarm was given a lot has changed. The first major change was the beginning of a COVID-19 pandemic on March 11, 2020. Many discoveries were made, from a better understanding of transmission, treatment, vaccines and challenges with new strains that arose after selective pressure

A comparative study between Germany and Italy in times before and during the Covid-19 pandemic

Em dezembro de 2019, ocorreu em Wuhan, China, surtos de uma nova pneumonia, o coronavírus (COVID-19). Em 11 de março a Organização Mundial da Saúda (OMS) declarou a COVID-19 como uma Pandemia. Cada país apresenta suas particularidades e estava preparado para enfrentar a pandemia de diferentes maneiras. O objetivo desse estudo é apresentar os prováveis motivos que levaram a Alemanha a enfrentar de maneira mais branda a pandemia em relação à Itália. Uma pesquisa sistemática foi feita nos centros de estatística dos países, Google Scholar e LitCovid. A Alemanha investe mais em saúde e tem mais leitos de Unidade de Terapia Intensiva (UTI) per 100000 capita do que a Itália. Os números de casos e mortes na Itália foram maiores do que o da Alemanha. A maioria dos casos da Itália são de pessoas idosas. Características culturais podem ter contribuído para a forma de contágio em cada país.In December 2019, outbreaks of new pneumonia occurred in Wuhan, China. the coronavirus disease (COVID-19). On March 11, the World Health Organization (WHO) registered COVID-19 as a pandemic. Each country has its particularities and was prepared to face a pandemic in different ways. The purpose of this study is to present the probable reasons that led Germany to confront a milder form of a pandemic in relation to Italy. A systematic searchs was carried out in the countries' statistical centers, Google Scholar and LitCovid. Germany invests more in health and has more Intensive Care Unit (ICU) beds per 100.000 inhabitants in Italy. The numbers of cases and deaths in Italy were higher than in Germany. Most cases in Italy are of elderly people. Cultural characteristics may have contributed to a form of contagion in each country