Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

Suzana BV Mello,1 Elaine R Tavares,2 Adriana Bulgarelli,2 Eloisa Bonf&aacute;,1 Raul C Maranh&atilde;o2,31Rheumatology Division, Faculdade de Medicina da Universidade de S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 2Lipid Metabolism Laboratory, the Heart Institute (INC...

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Autores principales:	Mello SB, Tavares ER, Bulgarelli A, Bonf&aacute; E, Maranh&atilde;o RC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/14cfb93a95e3450d80ac38a70c691f25
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spelling	oai:doaj.org-article:14cfb93a95e3450d80ac38a70c691f252021-12-02T02:42:32ZIntra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis1176-91141178-2013https://doaj.org/article/14cfb93a95e3450d80ac38a70c691f252013-02-01T00:00:00Zhttp://www.dovepress.com/intra-articular-methotrexate-associated-to-lipid-nanoemulsions-anti-in-a12216https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Suzana BV Mello,1 Elaine R Tavares,2 Adriana Bulgarelli,2 Eloisa Bonf&aacute;,1 Raul C Maranh&atilde;o2,31Rheumatology Division, Faculdade de Medicina da Universidade de S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 2Lipid Metabolism Laboratory, the Heart Institute (INCOR) of the Medical School Hospital, S&atilde;o Paulo, Brazil; 3Faculty of Pharmaceutical Sciences, University of S&atilde;o Paulo, S&atilde;o Paulo, BrazilObjective: Commercial methotrexate formulations (MTX) have poor anti-inflammatory action for intra-articular treatment of rheumatoid arthritis. Our aim was to investigate whether an association between methotrexate and lipidic nanoemulsions (LDE) could improve MTX intra-articular action.Methods: For its association to LDE, MTX was previously esterified with dodecyl bromide. LDE-MTX was prepared by high pressure homogenization. Antigen-induced arthritis (AIA) was achieved in rabbits sensitized with methylated bovine serum albumin, and the rabbits were subsequently intra-articularly injected with the antigen. Twenty-four hours after AIA induction, groups of four to nine rabbits were intra-articularly injected with increasing doses (0.0625&ndash;0.5 &micro;mol/kg) of LDE-MTX, and were compared to treatment with 0.5 &micro;mol/kg commercial MTX, LDE alone, and saline (controls). Synovial fluid was collected 48 hours after AIA induction for analysis of protein leakage and cell content. Synovial membranes were collected for histopathology. Uptake of LDE labeled with 3H-cholesteryl ether by the synovial tissue was also determined.Results: Uptake of radioactive LDE by arthritic joints was 2.5-fold greater than by normal joints. Treatment with intra-articular LDE-MTX elicited a clear dose response pattern by reducing the synovial leukocyte infiltrate (P = 0.004) and protein leakage (P = 0.032) when compared with arthritic non-treated joints. In contrast, the intra-articular injection of commercial MTX and LDE did not reduce leukocyte infiltrate or protein leakage. Toxicity to treatment was not observed in any of the animals.Conclusion: The association between LDE and MTX presented a marked anti-inflammatory effect that was absent after intra-articular commercial MTX treatment. Therefore, the new formulation is a candidate for future clinical studies.Keywords: nanoparticles, cholesterol, methotrexate, arthritis, antigen-induced arthritisMello SBTavares ERBulgarelli ABonf&aacute; EMaranh&atilde;o RCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 443-449 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Mello SB Tavares ER Bulgarelli A Bonf&aacute; E Maranh&atilde;o RC Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
description	Suzana BV Mello,1 Elaine R Tavares,2 Adriana Bulgarelli,2 Eloisa Bonf&aacute;,1 Raul C Maranh&atilde;o2,31Rheumatology Division, Faculdade de Medicina da Universidade de S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 2Lipid Metabolism Laboratory, the Heart Institute (INCOR) of the Medical School Hospital, S&atilde;o Paulo, Brazil; 3Faculty of Pharmaceutical Sciences, University of S&atilde;o Paulo, S&atilde;o Paulo, BrazilObjective: Commercial methotrexate formulations (MTX) have poor anti-inflammatory action for intra-articular treatment of rheumatoid arthritis. Our aim was to investigate whether an association between methotrexate and lipidic nanoemulsions (LDE) could improve MTX intra-articular action.Methods: For its association to LDE, MTX was previously esterified with dodecyl bromide. LDE-MTX was prepared by high pressure homogenization. Antigen-induced arthritis (AIA) was achieved in rabbits sensitized with methylated bovine serum albumin, and the rabbits were subsequently intra-articularly injected with the antigen. Twenty-four hours after AIA induction, groups of four to nine rabbits were intra-articularly injected with increasing doses (0.0625&ndash;0.5 &micro;mol/kg) of LDE-MTX, and were compared to treatment with 0.5 &micro;mol/kg commercial MTX, LDE alone, and saline (controls). Synovial fluid was collected 48 hours after AIA induction for analysis of protein leakage and cell content. Synovial membranes were collected for histopathology. Uptake of LDE labeled with 3H-cholesteryl ether by the synovial tissue was also determined.Results: Uptake of radioactive LDE by arthritic joints was 2.5-fold greater than by normal joints. Treatment with intra-articular LDE-MTX elicited a clear dose response pattern by reducing the synovial leukocyte infiltrate (P = 0.004) and protein leakage (P = 0.032) when compared with arthritic non-treated joints. In contrast, the intra-articular injection of commercial MTX and LDE did not reduce leukocyte infiltrate or protein leakage. Toxicity to treatment was not observed in any of the animals.Conclusion: The association between LDE and MTX presented a marked anti-inflammatory effect that was absent after intra-articular commercial MTX treatment. Therefore, the new formulation is a candidate for future clinical studies.Keywords: nanoparticles, cholesterol, methotrexate, arthritis, antigen-induced arthritis
format	article
author	Mello SB Tavares ER Bulgarelli A Bonf&aacute; E Maranh&atilde;o RC
author_facet	Mello SB Tavares ER Bulgarelli A Bonf&aacute; E Maranh&atilde;o RC
author_sort	Mello SB
title	Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
title_short	Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
title_full	Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
title_fullStr	Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
title_full_unstemmed	Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
title_sort	intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/14cfb93a95e3450d80ac38a70c691f25
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Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

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