Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Nanoparticles of LDE: A Potential Delivery Route for MTX in Sinovial Tissue of Antigen-Induced Arthritis.

Mello2,  Suzana B. V., Bonfa3,  Eloisa D. O., Valduga1,  Claudete J., Bugaralli1,  Adriana, Tavarez1,  Elaine R., Maranhao1,  Raul

Heart Institute (InCor), Faculdade de Medicina da Uiversidade de São Paulo
Reumatology Division, Faculdade de Medicina da Unversidade de São Paulo, São Paulo, Brazil
Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo


Methotrexate (MTX) remains the first choice in the management of rheumatoid arthritis (RA). Resistance to this drug is largely associated to MTX entry into the cell. Uptake of lipidic nanoemulsion has emerged as a new strategy for cancer chemotherapy since it carries drugs directed to affected tissue increasing its concentration with a reduced toxicity. The aim of the present study was therefore to evaluate the anti-inflammatory efficacy of a novel cholesterol-rich nanoemulsion coupled MTX (MTX-LDE) in antigen induced arthritis (AIA) in rabbits.


Toxicity, pharmacokinetics and biodistribution assays were performed. The dose-effect curve of the complex was also determined (0.05 – 0.4 mg/Kg of MTX-LDE). Arthritis (AIA) was induced in the knee joint of methylated serum albumin sensitized NZW rabbits. Twenty four hours after AIA induction animals were intravenously (IV) or intraarticularly (IA) injected with a single dose of commercial MTX (0.25 mg/Kg), LDE or saline. To give an equivalent dose of MTX-LDE, the amount of drug associated to the nanoemulsion was evaluated by HPLC prior the injection. Animals were sacrificed 48h after AIA induction when synovial fluid (SF) and membrane (SM) were collected. The inflammatory parameters analyzed were: total and differential leukocyte count, protein leakage in the SF and histopathological evaluation of SM.


MTX-LDE did not promote any hematological toxicity. The uptake of this complex was preferentially to liver, spleen and inflamed SM. MTX-LDE intravenously injected promoted a reduction of 65% of leukocyte infiltrate in the joint, and 41% in protein leakage and a significant reduction in the SM cell infiltrate. Likewise, the treatment with MTX-LDE by intraarticular route significantly reduced inflammatory parameters (table). In contrast, a single dose of commercial MTX, a DMARDs that requires several weeks to have a clinical effect, did not alter any evaluated parameter. LDE alone or saline were also ineffective (table).


Our study suggests that MTX-LDE is effective, well tolerated and exhibit a rapid effect, probably as a result of their good uptake by the synovial tissue. This novel therapeutic strategy represents a treatment option for RA.

# Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

TreatmentsnLeukocyte/mm3 of SFProtein leakage mg/ml of SF
AIA control1513514 ± 12545.31 ± 0.52
MTX-LDE (IV)94714 ± 415 (p = 0.000)3.17 ± 0.36 (p = 0.008)
MTX (IV)619450 ± 38966.87 ± 2.15
LDE (IV)617375 ± 15045.50 ± 1.28
MTX-LDE(IA)98416 ± 997 (p = 0.010)3.37 ± 0.63 (p = 0.029)
MTX (IA)418750 ± 21254.24 ± 0.34
Results are expressed as mean ± SE, p by comparison with control values

To cite this abstract, please use the following information:
Mello, Suzana B. V., Bonfa, Eloisa D. O., Valduga, Claudete J., Bugaralli, Adriana, Tavarez, Elaine R., Maranhao, Raul; Nanoparticles of LDE: A Potential Delivery Route for MTX in Sinovial Tissue of Antigen-Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :284
DOI: 10.1002/art.28053

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