Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury

Detalhes bibliográficos
Autor(a) principal: Santos, Luís Filipe Pereira dos
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/55510
Resumo: Tese de mestrado, Bioquímica (Bioquímica Médica), 2022, Universidade de Lisboa, Faculdade de Ciências
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spelling Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion InjuryQuercetinaRotenonaStress OxidativoLipossomasLesão por Isquemia e Reperfusão HepáticaTeses de mestrado - 2022Departamento de Química e BioquímicaTese de mestrado, Bioquímica (Bioquímica Médica), 2022, Universidade de Lisboa, Faculdade de CiênciasHepatic Ischemia and Reperfusion Injury, a medical condition derived from Hepatic Ischemia and Reperfusion, a clinical phenomenon commonly associated with medical interventions, such as a hepatic resection, is a very complex biological process that is associated with poor hepatic functional recovery, mortality and morbidity in humans. This complex process has numerous variables that can influence the outcome of existing treatments, which can only mitigate partially the damage. A possible treatment option is the administration of natural compounds extracted from plants that display antioxidant and/or anti-inflammatory properties, both of which are hallmarks of Hepatic Ischemia and Reperfusion Injury, such as resveratrol, curcumin, or quercetin. Quercetin not only displays these properties but also has protective effects against Hepatic Ischemia and Reperfusion Injury in rats. However, there are some drawbacks to quercetin’s administration in humans, such as low bioavailability, lack of systematic data about quercetin as a nutraceutical in humans and the existence of side effects and drug interactions as a supplement, all of which can possibly limit quercetin’s use. For that reason, the main goal of this research project is to discover a viable solution to overcome some of quercetin’s administration issues by incorporating quercetin into a liposomal formulation. To develop this quercetin liposomal formulation, it was first determined the optimal quercetin-to-lipid molar ratio to use for the formulation preparation, using a saturation curve of the incorporation of quercetin in the lipid bilayer of the liposomes. Preliminary data from this saturation curve indicated that the optimal quercetin-to-lipid molar ratio to be used was 1:10 (mol/mol). Next, the effect of free quercetin and the optimal quercetin liposomal formulation were compared for their effect against oxidative stress and toxicity caused by rotenone, a Complex I mitochondrial respiratory chain inhibitor, in C6 rat glioma cells. Cell viability was analyzed after 24 and 48 hours of rotenone incubation and oxidative stress after 4 and 16 hours of incubation, using MTT Assays and Flow Cytometry, respectively. Preliminary results indicated that, although neither quercetin form had any protective effect against rotenone-induced toxicity, both quercetin forms reduced similarly rotenone-induced oxidative stress. These preliminary results suggest that, in vitro, quercetin can be a good treatment option for conditions that involve oxidative stress and that this liposomal formulation can be a viable solution for quercetin cell delivery. Ultimately, these results suggest that the developed quercetin liposomal formulation is a possible pharmacological treatment for Hepatic Ischemia and Reperfusion Injury. However, this in vitro cell model does not reflect the entirety of the Hepatic Ischemia and Reperfusion Injury process and the biological clearance mechanisms for liposomal formulation. For that reason, it is required to conduct further studies to evaluate if this quercetin liposomal formulation can be a viable pharmacological treatment for Hepatic Ischemia and Reperfusion Injury.Corvo, Maria Luísa Teixeira de Azevedo Rodrigues, 1960-Herrera García, Federico, 1977-Repositório da Universidade de LisboaSantos, Luís Filipe Pereira dos2022-12-27T13:13:40Z202220222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/55510enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:02:32Zoai:repositorio.ul.pt:10451/55510Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:10.182968Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
title Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
spellingShingle Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
Santos, Luís Filipe Pereira dos
Quercetina
Rotenona
Stress Oxidativo
Lipossomas
Lesão por Isquemia e Reperfusão Hepática
Teses de mestrado - 2022
Departamento de Química e Bioquímica
title_short Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
title_full Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
title_fullStr Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
title_full_unstemmed Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
title_sort Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
author Santos, Luís Filipe Pereira dos
author_facet Santos, Luís Filipe Pereira dos
author_role author
dc.contributor.none.fl_str_mv Corvo, Maria Luísa Teixeira de Azevedo Rodrigues, 1960-
Herrera García, Federico, 1977-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Santos, Luís Filipe Pereira dos
dc.subject.por.fl_str_mv Quercetina
Rotenona
Stress Oxidativo
Lipossomas
Lesão por Isquemia e Reperfusão Hepática
Teses de mestrado - 2022
Departamento de Química e Bioquímica
topic Quercetina
Rotenona
Stress Oxidativo
Lipossomas
Lesão por Isquemia e Reperfusão Hepática
Teses de mestrado - 2022
Departamento de Química e Bioquímica
description Tese de mestrado, Bioquímica (Bioquímica Médica), 2022, Universidade de Lisboa, Faculdade de Ciências
publishDate 2022
dc.date.none.fl_str_mv 2022-12-27T13:13:40Z
2022
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/55510
url http://hdl.handle.net/10451/55510
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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