Alexandra Moreira

Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice

Publisher: American Scientific Publishers

Date: 12-2015

DOI: 10.1166/JBN.2015.2170

Abstract: 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 β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β 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 β. 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.

University Of Lisbon

Location: Portugal

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University Of Oxford

Location: United Kingdom of Great Britain and Northern Ireland

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I3S - Instituto De Investigação E Inovação Em Saúde, Universidade Do Porto

Location: Portugal

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IBMC

Location: Portugal

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ICBAS - Universidade Do Porto Instituto De Ciências Biomédicas Abel Salazar

Location: Portugal

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