Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/75661 |
Resumo: | Methotrexate (MTX) is first-line therapy for the treatment of rheumatoid arthritis (RA), however, its use may be limited by side effects notably post-injection malaise. When patients are intolerant or become unresponsive, second-line or antibody therapy may be indicated. A folate-targeted liposomal formulation of MTX (FL-MTX) is tropic to arthritic paws and prevents the onset of collagen-induced arthritis (CIA) in the mouse. We optimized the drug-to-lipid molar ratio to 0.15 and demonstrated the therapeutic efficacy of this form at 2 mg/kg MTX intraperitoneal (i.p.) twice a week. These improved liposomes were present in inflamed joints in proportion to the degree of swelling of the paw and bone remodeling activity. FL-MTX had lower hepatic and renal elimination of MTX than the free substance. FL-MTX provided equivalent results when given i.p. or subcutaneous (s.c.) and FL-MTX 2 mg/kg (drug/lipid 0.15), twice weekly, was similar to or more effective than 35 mg/kg MTX (same route and schedule) in reducing the incidence and swelling in the murine CIA model. These results suggest that FL-MTX is a more potent nanotherapeutic formulation than free MTX treatment. Its potential benefits for patients may include reduced frequency of treatment and lower overall doses for a given response. |
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Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritisLiposomesMethotrexateFolate-targetingRheumatoid arthritisCollagen-induced arthritisScience & TechnologyMethotrexate (MTX) is first-line therapy for the treatment of rheumatoid arthritis (RA), however, its use may be limited by side effects notably post-injection malaise. When patients are intolerant or become unresponsive, second-line or antibody therapy may be indicated. A folate-targeted liposomal formulation of MTX (FL-MTX) is tropic to arthritic paws and prevents the onset of collagen-induced arthritis (CIA) in the mouse. We optimized the drug-to-lipid molar ratio to 0.15 and demonstrated the therapeutic efficacy of this form at 2 mg/kg MTX intraperitoneal (i.p.) twice a week. These improved liposomes were present in inflamed joints in proportion to the degree of swelling of the paw and bone remodeling activity. FL-MTX had lower hepatic and renal elimination of MTX than the free substance. FL-MTX provided equivalent results when given i.p. or subcutaneous (s.c.) and FL-MTX 2 mg/kg (drug/lipid 0.15), twice weekly, was similar to or more effective than 35 mg/kg MTX (same route and schedule) in reducing the incidence and swelling in the murine CIA model. These results suggest that FL-MTX is a more potent nanotherapeutic formulation than free MTX treatment. Its potential benefits for patients may include reduced frequency of treatment and lower overall doses for a given response.This work has received funding from the European Union Horizon 2020 research and innovation program under grant agreement NMP-06-2015-683356 FOLSMART. This study was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145- FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020— Programa Operacional Regional do Norte. Diana Guimarães (SFRH/BD/140321/2018) holds a scholarship from FCT. Nuclear imaging was performed at CNRS, TAAM UPS44, In Vivo Imaging Centre for Preclinical and Translational Research CIPA, 45071, Orléans, France.info:eu-repo/semantics/publishedVersionMDPIUniversidade do MinhoGuimarães, Diana Isabel PereiraLager, FranckRenault, GillesGuezguez, JamilBurnet, MichaelCunha, JoanaCavaco-Paulo, ArturNogueira, Eugénia2022-01-212022-01-21T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/75661engGuimarães, D.; Lager, F.; Renault, G.; Guezguez, J.; Burnet, M.; Cunha, J.; Cavaco-Paulo, A.; Nogueira, E. Folate-Targeted Liposomal Formulations Improve Effects of Methotrexate in Murine Collagen-Induced Arthritis. Biomedicines 2022, 10, 229. https://doi.org/10.3390/biomedicines100202292227-905910.3390/biomedicines10020229https://www.mdpi.com/2227-9059/10/2/229info: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:RCAAP2023-07-21T12:50:07Zoai:repositorium.sdum.uminho.pt:1822/75661Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:48:46.156430Repositório 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 |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
title |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
spellingShingle |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis Guimarães, Diana Isabel Pereira Liposomes Methotrexate Folate-targeting Rheumatoid arthritis Collagen-induced arthritis Science & Technology |
title_short |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
title_full |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
title_fullStr |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
title_full_unstemmed |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
title_sort |
Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
author |
Guimarães, Diana Isabel Pereira |
author_facet |
Guimarães, Diana Isabel Pereira Lager, Franck Renault, Gilles Guezguez, Jamil Burnet, Michael Cunha, Joana Cavaco-Paulo, Artur Nogueira, Eugénia |
author_role |
author |
author2 |
Lager, Franck Renault, Gilles Guezguez, Jamil Burnet, Michael Cunha, Joana Cavaco-Paulo, Artur Nogueira, Eugénia |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Guimarães, Diana Isabel Pereira Lager, Franck Renault, Gilles Guezguez, Jamil Burnet, Michael Cunha, Joana Cavaco-Paulo, Artur Nogueira, Eugénia |
dc.subject.por.fl_str_mv |
Liposomes Methotrexate Folate-targeting Rheumatoid arthritis Collagen-induced arthritis Science & Technology |
topic |
Liposomes Methotrexate Folate-targeting Rheumatoid arthritis Collagen-induced arthritis Science & Technology |
description |
Methotrexate (MTX) is first-line therapy for the treatment of rheumatoid arthritis (RA), however, its use may be limited by side effects notably post-injection malaise. When patients are intolerant or become unresponsive, second-line or antibody therapy may be indicated. A folate-targeted liposomal formulation of MTX (FL-MTX) is tropic to arthritic paws and prevents the onset of collagen-induced arthritis (CIA) in the mouse. We optimized the drug-to-lipid molar ratio to 0.15 and demonstrated the therapeutic efficacy of this form at 2 mg/kg MTX intraperitoneal (i.p.) twice a week. These improved liposomes were present in inflamed joints in proportion to the degree of swelling of the paw and bone remodeling activity. FL-MTX had lower hepatic and renal elimination of MTX than the free substance. FL-MTX provided equivalent results when given i.p. or subcutaneous (s.c.) and FL-MTX 2 mg/kg (drug/lipid 0.15), twice weekly, was similar to or more effective than 35 mg/kg MTX (same route and schedule) in reducing the incidence and swelling in the murine CIA model. These results suggest that FL-MTX is a more potent nanotherapeutic formulation than free MTX treatment. Its potential benefits for patients may include reduced frequency of treatment and lower overall doses for a given response. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-21 2022-01-21T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/75661 |
url |
http://hdl.handle.net/1822/75661 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Guimarães, D.; Lager, F.; Renault, G.; Guezguez, J.; Burnet, M.; Cunha, J.; Cavaco-Paulo, A.; Nogueira, E. Folate-Targeted Liposomal Formulations Improve Effects of Methotrexate in Murine Collagen-Induced Arthritis. Biomedicines 2022, 10, 229. https://doi.org/10.3390/biomedicines10020229 2227-9059 10.3390/biomedicines10020229 https://www.mdpi.com/2227-9059/10/2/229 |
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.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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