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

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art_MELLO_Intra_articular_methotrexate_associated_to_lipid_nanoemulsions_anti_2013.PDF (571.95 KB)
Citações na Scopus
40
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
DOVE MEDICAL PRESS LTD
Autores
BULGARELLI, Adriana
Citação
INTERNATIONAL JOURNAL OF NANOMEDICINE, v.8, p.443-449, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 mu mol/kg) of LDE-MTX, and were compared to treatment with 0.5 mu 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 H-3-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.
Palavras-chave
nanoparticles, cholesterol, methotrexate, arthritis, antigen-induced arthritis
URI
https://observatorio.fm.usp.br/handle/OPI/1785
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/17
Artigos e Materiais de Revistas Científicas - LIM/31