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Advisor(s)
Abstract(s)
As vacinas, sĆ£o ferramentas indispensĆ”veis no combate a doenƧas, que sem a existĆŖncia
destas seriam altamente letais. Com o avanƧo do conhecimento cientĆfico, diferentes
tipos de vacinas foram desenvolvidos, sempre com o objetivo de proteger o ser humano
e alguns animais de diversas patologias que foram surgindo ao longo da histĆ³ria. Mais
recentemente, a comunidade cientĆfica, tem olhado para os Ć”cidos nucleicos,
nomeadamente para o RNA mensageiro (mRNA), como uma aposta segura e eficaz na
entrega do antigĆ©nio de interesse, como Ć© discutido no CapĆtulo I da dissertaĆ§Ć£o.
Com o aparecimento de novos vĆrus, como foi o caso do vĆrus respiratĆ³rio responsĆ”vel
pela COVID-19, o SARS-CoV-2, o qual se disseminou por todo o mundo, foi necessƔrio o
desenvolvimento de uma vacina capaz de desacelerar o avanƧo epidemiolĆ³gico e
diminuir o nĆŗmero de internamentos e morte de pessoas infetadas. A tecnologia do
mRNA como molĆ©cula codificadora do antigĆ©nio, aliado Ć formulaĆ§Ć£o de nanopartĆculas
lipĆdicas, levou Ć elaboraĆ§Ć£o de duas vacinas, uma criada pela Moderna e outra pela
Pfizer/BioNTech. Estas vacinas provaram ser eficazes e seguras, no entanto, quanto Ć
sua conservaĆ§Ć£o e transporte, as mesmas, teriam de ser transportadas em cadeia
ultrafria, o que nem sempre Ć© possĆvel ou viĆ”vel, quando se trata de um meio com
elevadas condicionantes econĆ³micas. Por isso, e com vista a melhorar a estabilidade
tƩrmica do mRNA foram estudados vƔrios mƩtodos onde essa estabilidade pudesse ser
assegurada. Pensou-se em fazer algumas alteraƧƵes na estrutura fĆsica e quĆmica do RNA,
reformular as partĆculas lipĆdicas de modo a diminuir a Ć”gua presente no nĆŗcleo da
nanopartĆcula, e por fim, o freeze-drying ou a liofilizaĆ§Ć£o.
Concluiu-se que a liofilizaĆ§Ć£o Ć© a alternativa mais eficaz e segura de melhorar a
termoestabilidade do mRNA, pois nĆ£o sĆ³ o complexo LNP/mRNA nĆ£o sofre alteraĆ§Ć£o
significativa de tamanho e forma durante o processo de freeze-drying, mas tambƩm a
conservaĆ§Ć£o pode ser feita a uma temperatura de 4 Ā°C, sem haver a necessidade de uma
cadeia ultrafria. Com isto, o alcance deste tipo de vacinas poderĆ” vir a ser superior, mais
econĆ³mico e com menor constrangimento logĆstico, levando a um melhoramento da
qualidade de vida e saĆŗde da populaĆ§Ć£o global.
O CapĆtulo II Ć© o resultado do estĆ”gio realizado em FarmĆ”cia ComunitĆ”ria, que decorreu
na FarmĆ”cia Moderna, na cidade da Guarda, no perĆodo de 22 de fevereiro a 1 de julho
de 2021, sob a orientaĆ§Ć£o da Dr.ĀŖ Ana Raquel Andrade. Neste capĆtulo encontra-se
descrita toda a minha experiĆŖncia profissional, desde o funcionamento da farmĆ”cia Ć
apresentaĆ§Ć£o das tarefas e atividades desempenhadas ao longo deste perĆodo.
Vaccines are indispensable tools in the fight against diseases, which without them would be highly lethal. With the advancement of scientific knowledge, many different types of vaccines have been developed, always with the aim of covering and protecting humans and some animals from various pathologies that have emerged throughout history. More recently, the scientific community has looked to nucleic acids, namely messenger RNA, as a safe and effective alternative for delivering the antigen of interest, as discussed in Chapter I of this Thesis. With the emergence of new viruses, such as the respiratory virus responsible for COVID19, SARS-CoV-2, which spread throughout the world, it was necessary to develop a vaccine capable of slowing down the epidemiological advance and decrease the number of hospitalizations and deaths. The mRNA technology as a molecule that holds the virus antigen, combined with the formulation of lipid nanoparticles, led to the development of two vaccines, one created by Moderna and the other by Pfizer/BioNTech. These vaccines proved to be effective and safe, however, in terms of their conservation and transport, they would have to be distributed in an ultra-cold chain, which is not always possible or feasible when it comes to low incoming countries. Therefore, and with a view to improving thermal stability, several strategies were studied, where this stability could be assured. It was thought of making some changes to the physical and chemical structure of RNA, reformulating the lipid particles to reduce the water present in the nanoparticle core, and finally, freeze-drying or lyophilization. It was concluded that lyophilization is the most effective and safe alternative to improve thermostability, since not only the LNP/mRNA complex does not undergo a significant change in size and shape during the freeze-drying process, but also conservation can be done at a temperature of 4 Ā°C, without the need for an ultra-cold chain. With this, the reach of this type of vaccines could be superior, more economical and with less logistical constraint, leading to an improvement in the quality of life and health of the global population. Chapter II is the result of the internship carried out in Community Pharmacy, which took place at FarmĆ”cia Moderna, in the city of Guarda, from February 22 to July 1, 2021, under the guidance of Dr. Ana Raquel Andrade. In this chapter, all my professional experience is described, from running the pharmacy to presenting the tasks and activities carried out during this period.
Vaccines are indispensable tools in the fight against diseases, which without them would be highly lethal. With the advancement of scientific knowledge, many different types of vaccines have been developed, always with the aim of covering and protecting humans and some animals from various pathologies that have emerged throughout history. More recently, the scientific community has looked to nucleic acids, namely messenger RNA, as a safe and effective alternative for delivering the antigen of interest, as discussed in Chapter I of this Thesis. With the emergence of new viruses, such as the respiratory virus responsible for COVID19, SARS-CoV-2, which spread throughout the world, it was necessary to develop a vaccine capable of slowing down the epidemiological advance and decrease the number of hospitalizations and deaths. The mRNA technology as a molecule that holds the virus antigen, combined with the formulation of lipid nanoparticles, led to the development of two vaccines, one created by Moderna and the other by Pfizer/BioNTech. These vaccines proved to be effective and safe, however, in terms of their conservation and transport, they would have to be distributed in an ultra-cold chain, which is not always possible or feasible when it comes to low incoming countries. Therefore, and with a view to improving thermal stability, several strategies were studied, where this stability could be assured. It was thought of making some changes to the physical and chemical structure of RNA, reformulating the lipid particles to reduce the water present in the nanoparticle core, and finally, freeze-drying or lyophilization. It was concluded that lyophilization is the most effective and safe alternative to improve thermostability, since not only the LNP/mRNA complex does not undergo a significant change in size and shape during the freeze-drying process, but also conservation can be done at a temperature of 4 Ā°C, without the need for an ultra-cold chain. With this, the reach of this type of vaccines could be superior, more economical and with less logistical constraint, leading to an improvement in the quality of life and health of the global population. Chapter II is the result of the internship carried out in Community Pharmacy, which took place at FarmĆ”cia Moderna, in the city of Guarda, from February 22 to July 1, 2021, under the guidance of Dr. Ana Raquel Andrade. In this chapter, all my professional experience is described, from running the pharmacy to presenting the tasks and activities carried out during this period.
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Keywords
FarmĆ”cia ComunitĆ”ria LiofilizaĆ§Ć£o Mrna Termoestabilidade Vacinas