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Targeting liver ischemia and reperfusion injury: nanoformulations for advanced drug/gene delivery

2023-05Doctoral thesis Open access
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datacite.subject.fosCiências Médicas::Medicina Básicapt_PT
dc.contributor.advisorCorvo, Maria Luísa Teixeira de Azevedo Rodrigues
dc.contributor.advisorFernandes, Eduarda das Graças Rodrigues
dc.contributor.advisorFernandes, Maria Alexandra Núncio de Carvalho Ramos
dc.contributor.authorFerreira-Silva, Margarida
dc.date.accessioned2024-06-03T09:06:23Z
dc.date.available2025-06-01T00:31:33Z
dc.date.issued2023-05
dc.date.submitted2023-01
dc.description.abstractHepatic ischemia and reperfusion injury (IRI) is an acute inflammatory process that may result from surgical interventions, such as liver resection or transplantation. This pathology has become a severe clinical issue, due to the increased incidence of hepatic cancer and the high number of liver transplants. So far, effective treatments have not been implemented, being crucial the development of new approaches. Drug delivery nanosystems have proved to be a major asset in therapy because of their ability to optimize drug delivery. In this work, distinct nanosystems were proposed to tackle the disadvantages of the existent treatments: anti-inflammatory-loaded long-circulating liposomes (ibuprofen, indomethacin or quercetin) or gold nanoparticles functionalized with poly(ethylene glycol) (PEG) and antisense oligonucleotides specific for silencing human TNFA gene (AuNPs_TNF-α) associated or not with liposomes. All nanosystems were characterized in terms of their physicochemical properties and stability. The in vitro therapeutic effect of quercetin liposomes was assessed in a hypoxia chamber model, where a decrease in pro-inflammatory biomarkers expression was observed. Using an in vivo hepatic IRI model, quercetin liposomes showed an anti-inflammatory effect and promoted hepatic lesions recovery. The association of AuNPs_TNF-α with liposomes was successfully accomplished but distinct methodologies were required to enhance their association. The in vitro anti-inflammatory effect of free and liposomal AuNPs_TNF-α was evaluated. When inflamed cells were treated with 25 nM of ASO using liposomal AuNPs_TNF-α, no silencing effect was observed and a 11-15% reduction in cellular viability was obtained. When an ASO concentration of 240 nM was used, 4 h or 6 h incubation with free AuNPs_TNF-α resulted in a decrease in TNF-α mRNA expression of 18% and 59%, respectively, without cytotoxic effects. In conclusion, the results suggested that quercetin liposomes and AuNPs_TNF-α might be potential therapeutic strategies to improve hepatic IRI treatment, overcoming the drawbacks presented by currently used therapies.pt_PT
dc.description.provenanceSubmitted by Paula Guerreiro (passarinho@reitoria.ulisboa.pt) on 2024-05-24T13:36:43Z No. of bitstreams: 1 scnd990026354741664_td_Ana_Silva.pdf: 5465046 bytes, checksum: b50af9d0663a2c2d487db2e2f15fe55f (MD5)en
dc.description.provenanceMade available in DSpace on 2024-06-03T09:06:23Z (GMT). No. of bitstreams: 1 scnd990026354741664_td_Ana_Silva.pdf: 5465046 bytes, checksum: b50af9d0663a2c2d487db2e2f15fe55f (MD5) Previous issue date: 2023-05en
dc.description.sponsorshipCOMPETE POCI-01-0145-FEDER-029253pt_PT
dc.description.sponsorshipPhospholipid Research Center - LCO-2017-052/1-1pt_PT
dc.identifier.tid101646984pt_PT
dc.identifier.urihttp://hdl.handle.net/10451/64955
dc.language.isoengpt_PT
dc.relationUID/DTP/04138/2020pt_PT
dc.relationResearch Institute for Medicines
dc.relationApplied Molecular Biosciences Unit
dc.relationApplied Molecular Biosciences Unit
dc.relationInstitute for Health and Bioeconomy
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.subjectlesão induzida por isquémia e reperfusão hepáticapt_PT
dc.subjectlipossomaspt_PT
dc.subjectnanopartículas de ouropt_PT
dc.subjectquercetinapt_PT
dc.subjectoligonucleótidos antisensept_PT
dc.subjecthepatic ischemia and reperfusion injurypt_PT
dc.subjectliposomespt_PT
dc.subjectgold nanoparticlespt_PT
dc.subjectquercetinpt_PT
dc.subjectantisense oligonucleotidespt_PT
dc.titleTargeting liver ischemia and reperfusion injury: nanoformulations for advanced drug/gene deliverypt_PT
dc.typedoctoral thesis
dspace.entity.typePublication
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleInstitute for Health and Bioeconomy
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F135264%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0140%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT
oaire.fundingStreamOE
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameFerreira Silva
person.givenNameMargarida
person.identifier.ciencia-id3010-D7CA-D2B9
person.identifier.orcid0000-0002-5724-2823
person.identifier.scopus-author-id57211577334
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.contributor.authoremailrepositorio@reitoria.ulisboa.pt
rcaap.rightsopenAccesspt_PT
rcaap.typedoctoralThesispt_PT
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thesis.degree.nameTese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2023pt_PT

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