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

Show simple item record

dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author MELLO, Suzana B. V. FMUSP-HC
TAVARES, Elaine R. FMUSP-HC
BULGARELLI, Adriana
BONFA, Eloisa FMUSP-HC
MARANHAO, Raul C. FMUSP-HC
dc.date.issued 2013
dc.identifier.citation INTERNATIONAL JOURNAL OF NANOMEDICINE, v.8, p.443-449, 2013
dc.identifier.issn 1178-2013
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/1785
dc.description.abstract 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.
dc.description.sponsorship · Fundacao do Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, SP, Brazil
· Conselho Nacional de Ciencia e Tecnologia (CNPq)
· Federico Foundation (EB)
dc.language.iso eng
dc.publisher DOVE MEDICAL PRESS LTD
dc.relation.ispartof International Journal of Nanomedicine
dc.rights restrictedAccess
dc.subject nanoparticles; cholesterol; methotrexate; arthritis; antigen-induced arthritis
dc.subject.other cholesterol-rich nanoemulsions; rheumatoid-arthritis; in-vivo; rabbits; emulsion; delivery; neutrophils; injection; strategy; leukemia
dc.title Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis
dc.type article
dc.rights.holder Copyright DOVE MEDICAL PRESS LTD
dc.description.group LIM/17
dc.description.group LIM/31
dc.identifier.doi 10.2147/IJN.S29392
dc.identifier.pmid 23439784
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author MELLO, Suzana B. V.:FM:MCM
hcfmusp.author TAVARES, Elaine R.:HC:INCOR
hcfmusp.author BONFA, Eloisa:FM:MCM
hcfmusp.author MARANHAO, Raul C.:HC:INCOR
hcfmusp.author.external · BULGARELLI, Adriana:Med Sch Hosp, Lipid Metab Lab, Heart Inst INCOR, Sao Paulo, Brazil
hcfmusp.origem.id 2-s2.0-84873944529
hcfmusp.origem.id WOS:000317922700042
hcfmusp.publisher.city ALBANY
hcfmusp.publisher.country NEW ZEALAND
hcfmusp.relation.reference · Ades A, 2001, GYNECOL ONCOL, V82, P84, DOI 10.1006/gyno.2001.6203
· Almeida CP, 2010, INT J NANOMED, V5, P679
· Braun J, 2009, CURR OPIN RHEUMATOL, V21, P216, DOI 10.1097/BOR.0b013e328329c79d
· Bulgarelli A, 2012, J CARDIOVASC PHARM, V59, P308, DOI 10.1097/FJC.0b013e318241c385
· Dervieux T, 2004, ARTHRITIS RHEUM, V50, P2766, DOI 10.1002/art.20460
· Doria AS, 2012, PEDIATR RADIOL, V42, P63, DOI 10.1007/s00247-011-2194-0
· FOLCH J, 1957, J BIOL CHEM, V226, P497
· FOONG WC, 1988, J PHARM PHARMACOL, V40, P464
· FOONG WC, 1993, J PHARM PHARMACOL, V45, P204
· Homma A, 2009, BIOORGAN MED CHEM, V17, P4647, DOI 10.1016/j.bmc.2009.04.063
· Lin YK, 2010, INT J NANOMED, V5, P117
· Lopez-Armada MJ, 2002, ANN RHEUM DIS, V61, P1027, DOI 10.1136/ard.61.11.1027
· Lo Prete AC, 2006, J PHARM PHARMACOL, V58, P801, DOI 10.1211/jpp.58.6.0010
· Madani SY, 2011, INT J NANOMED, V6, P2963, DOI 10.2147/IJN.S16923
· MARANHAO RC, 1994, CANCER RES, V54, P4660
· Maranhao RC, 2002, CANCER CHEMOTH PHARM, V49, P487, DOI 10.1007/s00280-002-0437-3
· Maranhao RC, 2008, ATHEROSCLEROSIS, V197, P959, DOI 10.1016/j.atherosclerosis.2007.12.051
· MARANHAO RC, 1992, BRAZ J MED BIOL RES, V25, P1003
· Mendes S, 2009, GYNECOL ONCOL, V112, P400, DOI 10.1016/j.ygyno.2008.10.018
· Moura JA, 2011, INT J NANOMED, V6, P2285, DOI 10.2147/IJN.S18039
· Padoveze AF, 2009, BRAZ J MED BIOL RES, V42, P172, DOI 10.1590/S0100-879X2009000200005
· Paliwal R, 2009, INT J PHARMACEUT, V380, P181, DOI 10.1016/j.ijpharm.2009.06.026
· Pimentel TA, 2011, LAB INVEST, V91, P33, DOI 10.1038/labinvest.2010.140
· Ranganathan P, 2006, ARTHRITIS RHEUM, V54, P1366, DOI 10.1002/art.21762
· Rodrigues DG, 2005, CANCER CHEMOTH PHARM, V55, P565, DOI 10.1007/s00280-004-0930-y
· Suarez-Almazor ME, 2000, COCHRANE DB SYST REV, V2
· Tavares ER, 2011, INT J NANOMED, V6, P2297, DOI 10.2147/IJN.S24048
· TERKELTAUB RA, 1991, J CLIN INVEST, V87, P20, DOI 10.1172/JCI114971
· Varatharajan N, 2009, INTERN MED J, V39, P228, DOI 10.1111/j.1445-5994.2009.01800.x
· WIGGINTON SM, 1980, ARTHRITIS RHEUM, V23, P119, DOI 10.1002/art.1780230121
· Williams AS, 2001, RHEUMATOLOGY, V40, P375, DOI 10.1093/rheumatology/40.4.375
dc.description.index MEDLINE
hcfmusp.citation.scopus 28
hcfmusp.affiliation.country Brasil
hcfmusp.scopus.lastupdate 2021-07-14


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace



Browse

My Account

Statistics