Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions

Intra-articular (IA) administration of drugs for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis is a common strategy; however, the rapid clearance from the synovial fluid restricts their effectivity due to the limited retention time. Drug Delivery Syst...

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Autores: Díez Villares, Sandra, García Varela, Lara, Groba de Antas, Soraya, Caeiro Rey, José Ramón, Carpintero-Fernandez, Paula, Mayán, María D., Aguiar Fernández, Pablo, Fuente, María de la
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:dnet:minerva_____::4fbfbc8f6ea6c0b04d6a21ebc0a245b9
Acesso em linha:https://hdl.handle.net/10347/47023
Access Level:acceso abierto
Palavra-chave:Intra-articular injection
Radiolabeled peptide
Senolytic peptide
PET imaging
Nanoemulsions
Drug delivery systems
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dc.title.none.fl_str_mv Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
title Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
spellingShingle Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
Díez Villares, Sandra
Intra-articular injection
Radiolabeled peptide
Senolytic peptide
PET imaging
Nanoemulsions
Drug delivery systems
title_short Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
title_full Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
title_fullStr Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
title_full_unstemmed Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
title_sort Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions
dc.creator.none.fl_str_mv Díez Villares, Sandra
García Varela, Lara
Groba de Antas, Soraya
Caeiro Rey, José Ramón
Carpintero-Fernandez, Paula
Mayán, María D.
Aguiar Fernández, Pablo
Fuente, María de la
author Díez Villares, Sandra
author_facet Díez Villares, Sandra
García Varela, Lara
Groba de Antas, Soraya
Caeiro Rey, José Ramón
Carpintero-Fernandez, Paula
Mayán, María D.
Aguiar Fernández, Pablo
Fuente, María de la
author_role author
author2 García Varela, Lara
Groba de Antas, Soraya
Caeiro Rey, José Ramón
Carpintero-Fernandez, Paula
Mayán, María D.
Aguiar Fernández, Pablo
Fuente, María de la
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)
dc.subject.none.fl_str_mv Intra-articular injection
Radiolabeled peptide
Senolytic peptide
PET imaging
Nanoemulsions
Drug delivery systems
topic Intra-articular injection
Radiolabeled peptide
Senolytic peptide
PET imaging
Nanoemulsions
Drug delivery systems
description Intra-articular (IA) administration of drugs for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis is a common strategy; however, the rapid clearance from the synovial fluid restricts their effectivity due to the limited retention time. Drug Delivery Systems (DDS) are currently being developed to increase their joint retention time. This study compares the biodistribution and retention time of a senolytic peptide (PEP), with potential application in osteoarthritis disease, and this senolytic peptide encapsulated in a DDS based on a lipid nanoemulsion (PEPsingle bondNE) by using positron emission tomography (PET) imaging. To this aim, the PEP was conjugated with a chelating agent (DFO) and radiolabeled with zirconium-89 (89Zr). Then, [89Zr]-PEP was encapsulated in a novel nanoemulsion formulation, composed by vitamin E, sphingomyelin, and a lipid-PEG. Afterward, healthy rats were administered with either the [89Zr]-PEP or the [89Zr]-PEP-NE via IA injection and underwent PET scans at 0.5-, 24-, 48-, 72-, 168-, 240- and 336 h post-injection. To assess the biodistribution of both radiotracers, several volume-of-interest were manually drawn in different organs of the rat body and the %ID/organ was calculated. The [89Zr]-PEP was successfully encapsulated in the NE and their physicochemical properties were minimally affected by the radiolabeling buffer. Adequate stability of both [89Zr]-PEP and [89Zr]-PEP-NE was found in synovial fluid over 72 h. Quantitative data from PET images revealed a significantly higher [89Zr]-PEP-NE retention in the injected knee than with [89Zr]-PEP in all follow-up PET scans. The [89Zr]-PEP %ID/organ values in the liver and kidney were significantly higher than those from [89Zr]-PEP-NE, which might indicate a faster elimination of the [89Zr]-PEP. Therefore, the study highlights the higher retention time on the target site of the [89Zr]-PEP-NE which may improve the therapeutic effects of the peptide. Thereby, the novel nanoemulsion formulation seems to be a successful DDS for IA injection. In addition, these results represent the first study that evaluates the distribution of a PET-guided DDS after its IA administration.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/47023
url https://hdl.handle.net/10347/47023
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII) AC18%2F00045 TARGETED MULTIFUNCTIONAL NANOEMULSIONS TO INTERRUPT METASTATIC PROGRESSION
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) AC21_2%2F00026 OASIS
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) AC21_2%2F00049 TRATAMIENTOS PERSONALIZADOS PARA LA OSTEOARTRITIS CON NANOFARMACOS CARGADOS DE PEPTIDOS SENOLITICOS Y ANTIINFLAMATORIOS
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI19%2F00145 FARMACOS DE NUEVA GENERACION BASADOS EN COMPUESTOS PEPTIDOMIMETICOS MODULADORES DE LAS CONEXINAS COMO AGENTES TERAPEUTICOS PARA RESTAURAR LA REGENERACION TISULAR EN PIEL Y CARTILAGO ARTICULAR.
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsionsDíez Villares, SandraGarcía Varela, LaraGroba de Antas, SorayaCaeiro Rey, José RamónCarpintero-Fernandez, PaulaMayán, María D.Aguiar Fernández, PabloFuente, María de laIntra-articular injectionRadiolabeled peptideSenolytic peptidePET imagingNanoemulsionsDrug delivery systemsIntra-articular (IA) administration of drugs for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis is a common strategy; however, the rapid clearance from the synovial fluid restricts their effectivity due to the limited retention time. Drug Delivery Systems (DDS) are currently being developed to increase their joint retention time. This study compares the biodistribution and retention time of a senolytic peptide (PEP), with potential application in osteoarthritis disease, and this senolytic peptide encapsulated in a DDS based on a lipid nanoemulsion (PEPsingle bondNE) by using positron emission tomography (PET) imaging. To this aim, the PEP was conjugated with a chelating agent (DFO) and radiolabeled with zirconium-89 (89Zr). Then, [89Zr]-PEP was encapsulated in a novel nanoemulsion formulation, composed by vitamin E, sphingomyelin, and a lipid-PEG. Afterward, healthy rats were administered with either the [89Zr]-PEP or the [89Zr]-PEP-NE via IA injection and underwent PET scans at 0.5-, 24-, 48-, 72-, 168-, 240- and 336 h post-injection. To assess the biodistribution of both radiotracers, several volume-of-interest were manually drawn in different organs of the rat body and the %ID/organ was calculated. The [89Zr]-PEP was successfully encapsulated in the NE and their physicochemical properties were minimally affected by the radiolabeling buffer. Adequate stability of both [89Zr]-PEP and [89Zr]-PEP-NE was found in synovial fluid over 72 h. Quantitative data from PET images revealed a significantly higher [89Zr]-PEP-NE retention in the injected knee than with [89Zr]-PEP in all follow-up PET scans. The [89Zr]-PEP %ID/organ values in the liver and kidney were significantly higher than those from [89Zr]-PEP-NE, which might indicate a faster elimination of the [89Zr]-PEP. Therefore, the study highlights the higher retention time on the target site of the [89Zr]-PEP-NE which may improve the therapeutic effects of the peptide. Thereby, the novel nanoemulsion formulation seems to be a successful DDS for IA injection. In addition, these results represent the first study that evaluates the distribution of a PET-guided DDS after its IA administration.ElsevierUniversidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e MedicinaUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)20232023-01-0120232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10347/47023reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII) AC18%2F00045 TARGETED MULTIFUNCTIONAL NANOEMULSIONS TO INTERRUPT METASTATIC PROGRESSIONInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) AC21_2%2F00026 OASISInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) AC21_2%2F00049 TRATAMIENTOS PERSONALIZADOS PARA LA OSTEOARTRITIS CON NANOFARMACOS CARGADOS DE PEPTIDOS SENOLITICOS Y ANTIINFLAMATORIOSInstituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI19%2F00145 FARMACOS DE NUEVA GENERACION BASADOS EN COMPUESTOS PEPTIDOMIMETICOS MODULADORES DE LAS CONEXINAS COMO AGENTES TERAPEUTICOS PARA RESTAURAR LA REGENERACION TISULAR EN PIEL Y CARTILAGO ARTICULAR.open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:minerva_____::4fbfbc8f6ea6c0b04d6a21ebc0a245b92026-06-15T12:47:27Z
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