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Development of Liposomal Formulations for Treatment of Hepatic Ischemia and Reperfusion Injury
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Resumo(s)
Hepatic 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.
Descrição
Tese de mestrado, Bioquímica (Bioquímica Médica), 2022, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Quercetina Rotenona Stress Oxidativo Lipossomas Lesão por Isquemia e Reperfusão Hepática Teses de mestrado - 2022