{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T13:26:32Z","timestamp":1777641992339,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["NMP-06-2015-683356 FOLSMART"],"award-info":[{"award-number":["NMP-06-2015-683356 FOLSMART"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04469\/2020"],"award-info":[{"award-number":["UIDB\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/140321\/2018"],"award-info":[{"award-number":["SFRH\/BD\/140321\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BioTecNorte","award":["NORTE-01-0145-FEDER-000004"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biomedicines10020229","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:32:52Z","timestamp":1642969972000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Folate-Targeted Liposomal Formulations Improve Effects of Methotrexate in Murine Collagen-Induced Arthritis"],"prefix":"10.3390","volume":"10","author":[{"given":"Diana","family":"Guimar\u00e3es","sequence":"first","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, University of Minho, 4710-055 Braga, Portugal"},{"name":"SOLFARCOS\u2014Pharmaceutical and Cosmetic Solutions, 4710-053 Braga, Portugal"}]},{"given":"Franck","family":"Lager","sequence":"additional","affiliation":[{"name":"INSERM\u2014Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1016, Institut Cochin, 75014 Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2273-1229","authenticated-orcid":false,"given":"Gilles","family":"Renault","sequence":"additional","affiliation":[{"name":"INSERM\u2014Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1016, Institut Cochin, 75014 Paris, France"}]},{"given":"Jamil","family":"Guezguez","sequence":"additional","affiliation":[{"name":"Synovo GmbH, Paul Ehrlich Str. 15, D-72076 T\u00fcbingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-5441","authenticated-orcid":false,"given":"Michael","family":"Burnet","sequence":"additional","affiliation":[{"name":"Synovo GmbH, Paul Ehrlich Str. 15, D-72076 T\u00fcbingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-7477","authenticated-orcid":false,"given":"Joana","family":"Cunha","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, University of Minho, 4710-055 Braga, Portugal"},{"name":"SOLFARCOS\u2014Pharmaceutical and Cosmetic Solutions, 4710-053 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-2064","authenticated-orcid":false,"given":"Artur","family":"Cavaco-Paulo","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, University of Minho, 4710-055 Braga, Portugal"},{"name":"SOLFARCOS\u2014Pharmaceutical and Cosmetic Solutions, 4710-053 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-245X","authenticated-orcid":false,"given":"Eug\u00e9nia","family":"Nogueira","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, University of Minho, 4710-055 Braga, Portugal"},{"name":"SOLFARCOS\u2014Pharmaceutical and Cosmetic Solutions, 4710-053 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s13105-012-0216-5","article-title":"Inflammation and rheumatoid arthritis","volume":"69","author":"Shrivastava","year":"2013","journal-title":"J. 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