Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/75661
Título: | Folate-targeted liposomal formulations improve effects of methotrexate in murine collagen-induced arthritis |
Autor(es): | Guimarães, Diana Isabel Pereira Lager, Franck Renault, Gilles Guezguez, Jamil Burnet, Michael Cunha, Joana Cavaco-Paulo, Artur Nogueira, Eugénia |
Palavras-chave: | Liposomes Methotrexate Folate-targeting Rheumatoid arthritis Collagen-induced arthritis |
Data: | 21-Jan-2022 |
Editora: | MDPI |
Revista: | Biomedicines |
Citação: | 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 |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/75661 |
DOI: | 10.3390/biomedicines10020229 |
ISSN: | 2227-9059 |
Versão da editora: | https://www.mdpi.com/2227-9059/10/2/229 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_55189_1.pdf | 2,66 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons