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Desenvolvimento de lipossomas para entrega intranasal de fármacos neuroprotetores em Acidente Vascular Cerebral isquémico
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Este trabalho representa o meu relatório final para a conclusão do Mestrado Integrado
em Ciências Farmacêuticas na Universidade da Beira Interior e está dividido em dois
capítulos.
O primeiro aborda a investigação laboratorial realizada no Centro de Investigação em
Ciências da Saúde da Universidade da Beira Interior, cujo objetivo foi desenvolver e
caracterizar formulações lipossomais contendo um fármaco convencional, de baixo peso
molecular e lipofílico, de ação neuroprotetora, com e sem DNA plasmídico, para
aplicação terapêutica no contexto do Acidente Vascular Cerebral isquémico,
privilegiando a via intranasal como estratégia de administração direcionada ao sistema
nervoso central. Os lipossomas foram preparados com diferentes fases aquosas e
proporções lipídicas, sendo caracterizados quanto ao tamanho, índice de polidispersão,
potencial zeta, encapsulação de DNA e estabilidade. Os resultados demonstraram que a
preparação em tampão fosfato 10 mM pH 7,2 foi a condição mais promissora para
formulações contendo DNA, enquanto a solução de NaCl 0,9% favoreceu a
homogeneidade em formulações sem DNA. A presença do lípido catiónico (DOTAP)
revelou-se essencial para a encapsulação de material genético, embora em elevadas
proporções tenha comprometido a obtenção de lipossomas sem DNA homogéneos. O
fármaco de baixo peso molecular até uma percentagem mássica de 15,4% não alterou
significativamente as propriedades físico-químicas dos lipossomas com DNA, mas uma
proporção mais elevada (20% m/m) levou à sua precipitação em lipossomas sem DNA
passado alguns dias, não tendo o mesmo sido verificado na percentagem de 11,1% (m/m).
Estes resultados confirmam o potencial dos lipossomas como sistema de encapsulação
de um fármaco de interesse em neuroproteção, associado ou não a DNA plasmídico,
tendo em vista a entrega de fármacos neuroprotetores em casos de AVC isquémico. No
entanto, ainda são necessários mais estudos, de modo a melhorar a estabilidade e estudar
a sua eficácia terapêutica.
O segundo capítulo diz respeito à minha experiência profissionalizante na vertente de
farmácia comunitária, cujo objetivo foi a aproximação à realidade da prática
farmacêutica, através do contacto direto com os utentes e da resolução de casos clínicos
reais. O estágio decorreu de fevereiro a junho de 2025, na Farmácia Gama Vieira em
Tondela, sob a orientação da Dra. Fátima Vale. Durante este período, participei em
diversas atividades da farmácia, nomeadamente a receção e conferência de encomendas, a dispensa de medicamentos, o aconselhamento farmacêutico e a preparação de
medicamentos manipulados. Neste capítulo relatei a minha experiência, abordando
temas como o funcionamento da farmácia, as atividades desempenhadas ao longo do
estágio, bem como as diferentes experiências ao nível do aconselhamento farmacêutico.
Este período proporcionou-me a oportunidade de integrar e aplicar os conhecimentos
teóricos obtidos ao longo do curso à prática profissional, assim como aprimorar
competências técnicas e humanas.
This work represents my final report for the completion of the Integrated Master’s Degree in Pharmaceutical Sciences at the University of Beira Interior and is divided into two chapters. The first chapter addresses the laboratory research carried out at the Health Sciences Research Centre of the University of Beira Interior, aiming to develop and characterize liposomal formulations containing a conventional, low molecular weight, lipophilic neuroprotective drug, with and without plasmid DNA, for therapeutic application in the context of ischemic stroke, prioritizing the intranasal route as a targeted strategy for central nervous system delivery. Liposomes were prepared using different aqueous phases and lipid ratios, and were characterized with respect to size, polydispersity index, zeta potential, DNA encapsulation and stability. The results demonstrated that preparation in 10 mM phosphate buffer at pH 7,2 was the most promising condition for formulations containing DNA, while 0,9% NaCl solution favored homogeneity in formulations without DNA. The presence of the cationic lipid (DOTAP) proved to be essential for genetic material encapsulation, although at high ratios it compromised the obtention of homogeneous DNA-free liposomes. The incorporation of the low molecular weight drug up to 15,4% (w/w) did not significantly alter the physicochemical properties of DNA-containing liposomes, but a higher proportion (20% w/w) led to drug precipitation in DNA-free liposomes after a few days, which was not observed at 11,1% (w/w). These findings confirm the potential of liposomes as carriers for a neuroprotective drug of interest, either associated with or without plasmid DNA, for the delivery of neuroprotective agents in ischemic stroke. Nevertheless, further studies are required to improve stability and assess therapeutic efficacy. The second chapter concerns my professional training experience in the field of community pharmacy, aiming at bridging academic knowledge with the reality of pharmaceutical practice through direct contact with patients and the management of real clinical cases. The internship took place from February to June 2025 at Farmácia Gama Vieira in Tondela, under the supervision of Dr. Fátima Vale. During this period, I participated in several pharmacy activities, including order reception and verification, medicine dispensing, pharmaceutical counseling and the preparation of compounded medications. In this chapter, I report my experience, addressing topics such as pharmacy organization, the activities performed throughout the internship and different experiences in pharmaceutical counseling. This period provided me with the opportunity to integrate and apply the theoretical knowledge acquired during the course into professional practice, as well as to refine both technical and interpersonal skills.
This work represents my final report for the completion of the Integrated Master’s Degree in Pharmaceutical Sciences at the University of Beira Interior and is divided into two chapters. The first chapter addresses the laboratory research carried out at the Health Sciences Research Centre of the University of Beira Interior, aiming to develop and characterize liposomal formulations containing a conventional, low molecular weight, lipophilic neuroprotective drug, with and without plasmid DNA, for therapeutic application in the context of ischemic stroke, prioritizing the intranasal route as a targeted strategy for central nervous system delivery. Liposomes were prepared using different aqueous phases and lipid ratios, and were characterized with respect to size, polydispersity index, zeta potential, DNA encapsulation and stability. The results demonstrated that preparation in 10 mM phosphate buffer at pH 7,2 was the most promising condition for formulations containing DNA, while 0,9% NaCl solution favored homogeneity in formulations without DNA. The presence of the cationic lipid (DOTAP) proved to be essential for genetic material encapsulation, although at high ratios it compromised the obtention of homogeneous DNA-free liposomes. The incorporation of the low molecular weight drug up to 15,4% (w/w) did not significantly alter the physicochemical properties of DNA-containing liposomes, but a higher proportion (20% w/w) led to drug precipitation in DNA-free liposomes after a few days, which was not observed at 11,1% (w/w). These findings confirm the potential of liposomes as carriers for a neuroprotective drug of interest, either associated with or without plasmid DNA, for the delivery of neuroprotective agents in ischemic stroke. Nevertheless, further studies are required to improve stability and assess therapeutic efficacy. The second chapter concerns my professional training experience in the field of community pharmacy, aiming at bridging academic knowledge with the reality of pharmaceutical practice through direct contact with patients and the management of real clinical cases. The internship took place from February to June 2025 at Farmácia Gama Vieira in Tondela, under the supervision of Dr. Fátima Vale. During this period, I participated in several pharmacy activities, including order reception and verification, medicine dispensing, pharmaceutical counseling and the preparation of compounded medications. In this chapter, I report my experience, addressing topics such as pharmacy organization, the activities performed throughout the internship and different experiences in pharmaceutical counseling. This period provided me with the opportunity to integrate and apply the theoretical knowledge acquired during the course into professional practice, as well as to refine both technical and interpersonal skills.
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Palavras-chave
Administração intranasal AVC isquémico Farmácia comunitária Lipossomas Neuroproteção Community pharmacy Intranasal administration Ischemic stroke Liposomes Neuroprotection