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Formulação e Caraterização de Lipossomas de Sinvastatina para o tratamento do cancro do pulmão por administração intravenosa
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| Documento em Acesso Embargado até dia 08-10-2028. Tente solicitar cópia ao autor carregando no ficheiro | 2.57 MB | Adobe PDF |
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Este relatório de estágio cuja a finalidade é a obtenção do grau de Mestre em Ciências Farmacêuticas foi realizado no âmbito da Unidade Curricular de 5º ano “Estágio” do Mestrado Integrado em Ciências Farmacêuticas da Universidade da Beira Interior – Covilhã. O documento encontra-se estruturado em dois capítulos: o primeiro refere-se à componente de investigação científica e o segundo relata a minha experiência profissionalizante em Farmácia Comunitária.
O Capítulo I, intitulado de “Formulação e Caraterização de Lipossomas de Sinvastatina para o tratamento do cancro do pulmão por administração intravenosa” foi desenvolvido no RISE-Health, Departamento de Ciências Médicas, Faculdade das Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal. O cancro do pulmão é a principal causa de morte oncológica no mundo. Um dos principais fatores que agravam a taxa de mortalidade é o diagnóstico tardio da doença, momento em que existem poucas alternativas terapêuticas eficazes. A sinvastatina, usada tradicionalmente no tratamento de dislipidemias, tem sido estudada para o tratamento de vários tipos de cancro. Contudo, as elevadas doses necessárias produzem efeitos secundários que limitam a sua utilização. O direcionamento da sinvastatina para os tumores seria importante para se alcançar segurança e eficácia nesta nova aplicação terapêutica. Neste contexto, o objetivo principal do trabalho de investigação foi desenvolver lipossomas de sinvastatina. Para a preparação dos lipossomas, os lípidos (fosfatidilcolina, colesterol, conjugado diestearoil fosfatidiletanolamina-polietilenoglicol 2000) e a sinvastatina foram dissolvidos num solvente orgânico, misturados, e adicionados à fase aquosa (cloreto de sódio 0,9%) sob agitação. Os lipossomas foram caraterizados pelo diâmetro hidrodinâmico, índice de polidispersão (PDI) e pela quantificação de sinvastatina e colesterol. Após remoção de agregados por centrifugação e esterilização por filtração, o produto final foi obtido com um rendimento superior a 95%, tamanho médio de 77 nm, PDI de 0,182, concentração de sinvastatina de 368 μM, dos quais praticamente 100% está associada aos lipossomas, e uma razão molar sinvastatina/lípido de 12,8%. Os resultados obtidos evidenciam um processo de preparação simples, reprodutível, elevada homogeneidade na formulação final, tamanho adequado a administração intravenosa e elevada eficiência de encapsulação. Futuramente, serão necessários estudos de estabilidade, bem como estudos in vitro e in vivo, de eficácia e segurança deste novo potencial medicamento.
O Capítulo II, descreve o estágio curricular em Farmácia Comunitária, realizado na Farmácia do Mosteiro, na Batalha, distrito Leiria, no período de 03 de fevereiro de 2025 a 20 de junho de 2025, com a orientação da Dr. Tânia Couto. Nesta secção, abordo de forma detalhada algumas das minhas experiências e todas as competências adquiridas na Farmácia do Mosteiro. Durante o período de estágio tive a oportunidade de desenvolver todas as atividades inerentes ao funcionamento diário de uma farmácia Comunitária, acompanhando o percurso completo do medicamento e de outros produtos de saúde. Deste modo, este segundo capítulo aborda detalhadamente a caraterização da Farmácia do Mosteiro e os serviços prestados, a receção e armazenamento de medicamentos e produtos de saúde, bem como a interação tripartida essencial para um bom farmacêutico comunitário, a interação entre o utente, o farmacêutico e o medicamento, essencial para uma prática profissional de qualidade. Ademais, o relatório de estágio descreve ainda alguns dos aconselhamentos que pude realizar, nomeadamente no âmbito de medicamento não sujeitos a receita médica de dispensa exclusiva em farmácia e de aconselhamento dermocosmético adequados às necessidades individuais de cada utente. O estágio na Farmácia do Mosteiro revelou-se, desde a fase inicial, uma experiência enriquecedora que permitiu consolidar os conhecimentos teóricos adquiridos no decorrer do Mestrado Integrado em Ciências Farmacêuticas e desenvolver soft skills essenciais ao quotidiano da farmácia Comunitária. Esta experiência profissionalizante reforçou, de forma clara, a minha consciência da importância do papel da farmácia Comunitária na promoção da saúde e no bem-estar da população.
This internship report whose purpose is to obtain a Master´s degree in Pharmaceutical Sciences was carried out within the scope of the fifth-year curricular unit “internship” of the Integrated Master’s Degree in Pharmaceutical Sciences at the University of Beira Interior – Covilhã. The document is divided in two chapters: the first addressing the scientific research component and second reporting my professionalizing experience on community pharmacy. Chapter I, labeled as “Formulation and Characterization of liposomal simvastatin for lung cancer treatment by intravenous administration” was executed in RISE-Health – Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Lung cancer remains the leading cause of oncologic deaths worldwide. One of the major factors that is associated with a higher mortality rate is a delayed diagnosis of the disease, at which point there are few effective therapeutics options. Simvastatin which traditionally used for dyslipidemia treatment, has been studied as a potential therapy for several types of cancer. However, the high doses required to produce the desire effect have an excessive secondary effect that restrain is application. Encapsulation and targeting of simvastatin for tumor cells would be crucial to achieve security and effectiveness in this new therapeutic application. In this context, the main objective of this project was to develop liposomal simvastatin. To prepare the liposomes, lipids (phosphatidylcholine, cholesterol, distearoyl phosphatidylethanolamine-polyethyleneglycol 2000 conjugate) and simvastatin, dissolved in an organic solvent, was added to aqueous phase. After removing aggregated particles by centrifugation and sterilized by filtration, the liposomes were characterized by hydrodynamic diameter, polydispersity index (PDI) by quantification of simvastatin and cholesterol. The final product was a mean size of 77nm, a PDI of 0,182, simvastatin dosage of 368 μM of which are approximately 100% are associated with liposomes and a mass ratio simvastatin/lipid of 12,8%. These results highlight a simple and reproducible preparation process, leading to a final formulation with a high homogeneity, an adequate mean size and a high encapsulation efficiency. Future studies should include stability assessments, as well in vitro and in vivo evaluations of efficacy and safety, in order to confirm the potential of this formulation as a novel anticancer therapeutic. Chapter II describes the curricular internship in community pharmacy, carried out at Farmácia Mosteiro, Batalha (Leiria district) between February 3rd and June 20th, 2025, under the guidance of Dr. Tânia Couto. This section provides a detailed account of my professional experiences and the skills acquired during the internship at Farmácia do Mosteiro. Throughout this period, I had the opportunity to develop all activities inherent to the daily functioning of a community pharmacy, following the complete path of medicines and other health products. Accordingly, this second chapter presents in detail the characterization of Farmácia do Mosteiro, the services provided to population, the reception and storage of medicines and health products, as well as the tripartite interaction essential to good pharmaceutical practice — the relationship between the patient, the pharmacist, and the medicine — which is fundamental to ensuring high-quality professional practice. In addition, the internship report describes several pharmaceutical counseling activities, particularly regarding non-prescription medicines exclusively dispensed in pharmacies (MNSRM-EF) and dermocosmetic counseling tailored to the individual needs of each patient. From the very beginning, the internship at Farmácia do Mosteiro proved to be an enriching and formative experience, allowing the consolidation of theoretical knowledge acquired during the Integrated Master’s Degree in Pharmaceutical Sciences, and the development of essential soft skills required in the daily routine of community pharmacy practice. This professional experience clearly reinforced the importance of the community pharmacy in promoting health and improving the well-being of the population.
This internship report whose purpose is to obtain a Master´s degree in Pharmaceutical Sciences was carried out within the scope of the fifth-year curricular unit “internship” of the Integrated Master’s Degree in Pharmaceutical Sciences at the University of Beira Interior – Covilhã. The document is divided in two chapters: the first addressing the scientific research component and second reporting my professionalizing experience on community pharmacy. Chapter I, labeled as “Formulation and Characterization of liposomal simvastatin for lung cancer treatment by intravenous administration” was executed in RISE-Health – Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Lung cancer remains the leading cause of oncologic deaths worldwide. One of the major factors that is associated with a higher mortality rate is a delayed diagnosis of the disease, at which point there are few effective therapeutics options. Simvastatin which traditionally used for dyslipidemia treatment, has been studied as a potential therapy for several types of cancer. However, the high doses required to produce the desire effect have an excessive secondary effect that restrain is application. Encapsulation and targeting of simvastatin for tumor cells would be crucial to achieve security and effectiveness in this new therapeutic application. In this context, the main objective of this project was to develop liposomal simvastatin. To prepare the liposomes, lipids (phosphatidylcholine, cholesterol, distearoyl phosphatidylethanolamine-polyethyleneglycol 2000 conjugate) and simvastatin, dissolved in an organic solvent, was added to aqueous phase. After removing aggregated particles by centrifugation and sterilized by filtration, the liposomes were characterized by hydrodynamic diameter, polydispersity index (PDI) by quantification of simvastatin and cholesterol. The final product was a mean size of 77nm, a PDI of 0,182, simvastatin dosage of 368 μM of which are approximately 100% are associated with liposomes and a mass ratio simvastatin/lipid of 12,8%. These results highlight a simple and reproducible preparation process, leading to a final formulation with a high homogeneity, an adequate mean size and a high encapsulation efficiency. Future studies should include stability assessments, as well in vitro and in vivo evaluations of efficacy and safety, in order to confirm the potential of this formulation as a novel anticancer therapeutic. Chapter II describes the curricular internship in community pharmacy, carried out at Farmácia Mosteiro, Batalha (Leiria district) between February 3rd and June 20th, 2025, under the guidance of Dr. Tânia Couto. This section provides a detailed account of my professional experiences and the skills acquired during the internship at Farmácia do Mosteiro. Throughout this period, I had the opportunity to develop all activities inherent to the daily functioning of a community pharmacy, following the complete path of medicines and other health products. Accordingly, this second chapter presents in detail the characterization of Farmácia do Mosteiro, the services provided to population, the reception and storage of medicines and health products, as well as the tripartite interaction essential to good pharmaceutical practice — the relationship between the patient, the pharmacist, and the medicine — which is fundamental to ensuring high-quality professional practice. In addition, the internship report describes several pharmaceutical counseling activities, particularly regarding non-prescription medicines exclusively dispensed in pharmacies (MNSRM-EF) and dermocosmetic counseling tailored to the individual needs of each patient. From the very beginning, the internship at Farmácia do Mosteiro proved to be an enriching and formative experience, allowing the consolidation of theoretical knowledge acquired during the Integrated Master’s Degree in Pharmaceutical Sciences, and the development of essential soft skills required in the daily routine of community pharmacy practice. This professional experience clearly reinforced the importance of the community pharmacy in promoting health and improving the well-being of the population.
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Palavras-chave
Administração intravenosa Cancro do Pulmão Farmácia Comunitária Lipossomas Sinvastatina Community Pharmacy Intravenous Administration Lipossomes Lung Cancer Simvastatin