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TitleEnhancing methotrexate tolerance with folate tagged liposomes in arthritic mice
Author(s)Nogueira, Eugénia Sofia Costa
Lager, Franck
Le Roux, Delphine
Nogueira, Patrícia
Freitas, Jaime
Charvet, Celine
Renault, Gilles
Loureiro, Ana
Almeida, Catarina R.
Ohradanova-Repic, Anna
Machacek, Christian
Bernardes, Gonçalo J. L.
Moreira, Alexandra
Stockinger, Hannes
Burnet, Michael
Carmo, Alexandre M.
Gomes, Andreia
Preto, Ana
Bismuth, Georges
Cavaco-Paulo, Artur
KeywordsRheumatoid Arthritis
Folate Receptor
Issue date18-Mar-2015
PublisherAmerican Scientific Publishers
JournalJournal of Biomedical Nanotechnology
CitationNogueira, E.; Lager, Franck; Le Roux, Delphine; Nogueira, Patrícia; Freitas, Jaime; Charvet, Celine; Renault, Gilles; Loureiro, A.; Almeida, Catarina R.; Ohradanova-Repic, Anna; Machacek, Christian; Bernardes, Gonçalo J. L.; Moreira, Alexandra; Stockinger, Hannes; Burnet, Michael; Carmo, Alexandre M.; Gomes, A. C.; Preto, A.; Bismuth, Georges; Paulo, Artur Cavaco, Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice. Journal of Biomedical Nanotechnology, 11(12), 2243-2252, 2015
Abstract(s)Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor . These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.
Publisher version
AccessOpen access
Appears in Collections:CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series
DBio - Artigos/Papers

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