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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMELLO, Suzana B. V.
dc.contributor.authorTAVARES, Elaine R.
dc.contributor.authorBULGARELLI, Adriana
dc.contributor.authorBONFA, Eloisa
dc.contributor.authorMARANHAO, Raul C.
dc.date.accessioned2013-09-23T16:36:12Z
dc.date.available2013-09-23T16:36:12Z
dc.date.issued2013
dc.description.abstractObjective: 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.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao do Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, SP, Brazil
dc.description.sponsorshipConselho Nacional de Ciencia e Tecnologia (CNPq)
dc.description.sponsorshipFederico Foundation (EB)
dc.identifier.citationINTERNATIONAL JOURNAL OF NANOMEDICINE, v.8, p.443-449, 2013
dc.identifier.doi10.2147/IJN.S29392
dc.identifier.issn1178-2013
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1785
dc.language.isoeng
dc.publisherDOVE MEDICAL PRESS LTD
dc.relation.ispartofInternational Journal of Nanomedicine
dc.rightsrestrictedAccess
dc.rights.holderCopyright DOVE MEDICAL PRESS LTD
dc.subjectnanoparticles
dc.subjectcholesterol
dc.subjectmethotrexate
dc.subjectarthritis
dc.subjectantigen-induced arthritis
dc.subject.othercholesterol-rich nanoemulsions
dc.subject.otherrheumatoid-arthritis
dc.subject.otherin-vivo
dc.subject.otherrabbits
dc.subject.otheremulsion
dc.subject.otherdelivery
dc.subject.otherneutrophils
dc.subject.otherinjection
dc.subject.otherstrategy
dc.subject.otherleukemia
dc.subject.wosNanoscience & Nanotechnology
dc.subject.wosPharmacology & Pharmacy
dc.titleIntra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalBULGARELLI, Adriana:Med Sch Hosp, Lipid Metab Lab, Heart Inst INCOR, Sao Paulo, Brazil
hcfmusp.citation.scopus40
hcfmusp.contributor.author-fmusphcSUZANA BEATRIZ VERISSIMO DE MELLO
hcfmusp.contributor.author-fmusphcELAINE RUFO TAVARES
hcfmusp.contributor.author-fmusphcELOISA SILVA DUTRA DE OLIVEIRA BONFA
hcfmusp.contributor.author-fmusphcRAUL CAVALCANTE MARANHAO
hcfmusp.description.beginpage443
hcfmusp.description.endpage449
hcfmusp.description.volume8
hcfmusp.origemWOS
hcfmusp.origem.pubmed23439784
hcfmusp.origem.scopus2-s2.0-84873944529
hcfmusp.origem.wosWOS:000317922700042
hcfmusp.publisher.cityALBANY
hcfmusp.publisher.countryNEW ZEALAND
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.remissive.sponsorshipFederico Foundation
hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.remissive.sponsorshipFederico Foundation
hcfmusp.scopus.lastupdate2024-05-10
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