Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

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

Authors Mello S, Tavares E, Bulgarelli A, Bonfá E, Maranhão R, Maria

Received 22 December 2011

Accepted for publication 2 July 2012

Published 14 February 2013 Volume 2013:8(1) Pages 443—449


Review by Single-blind

Peer reviewer comments 2

Suzana BV Mello,1 Elaine R Tavares,2 Adriana Bulgarelli,2 Eloisa Bonfá,1 Raul C Maranhão2,3

1Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 2Lipid Metabolism Laboratory, the Heart Institute (INCOR) of the Medical School Hospital, São Paulo, Brazil; 3Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

Objective: 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 (0.0625–0.5 µmol/kg) of LDE-MTX, and were compared to treatment with 0.5 µmol/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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats

Maranhão RC, Guido MC, de Lima AD, Tavares ER, Marques AF, Tavares de Melo MD, Nicolau JC, Salemi VMC, Kalil-Filho R

International Journal of Nanomedicine 2017, 12:3767-3784

Published Date: 17 May 2017

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Kretzer IF, Maria DA, Guido MC, Contente TC, Maranhão RC

International Journal of Nanomedicine 2016, 11:885-904

Published Date: 7 March 2016

Novel formulation of a methotrexate derivative with a lipid nanoemulsion

Moura JA, Valduga CJ, Tavares ER, Kretzer IF, Maria DA, Maranhao RC

International Journal of Nanomedicine 2011, 6:2285-2295

Published Date: 12 October 2011

Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

Tavares ER, Freitas FR, Diament JD, Maranhão RC

International Journal of Nanomedicine 2011, 6:2297-2304

Published Date: 12 October 2011

Readers of this article also read:

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Biomarkers for osteoarthritis: investigation, identification, and prognosis

Zhai G, Aref Eshghi E

Current Biomarker Findings 2012, 2:19-28

Published Date: 29 June 2012

Topical diclofenac in the treatment of osteoarthritis of the knee

Niklas Schuelert, Fiona A Russell, Jason J McDougall

Orthopedic Research and Reviews 2011, 3:1-8

Published Date: 6 February 2011