Effects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation

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dc.contributor.authorAlves, C. F.
dc.contributor.authorde Melo, N. F. S. [UNESP]
dc.contributor.authorFraceto, L. F. [UNESP]
dc.contributor.authorde Araujo, D. R.
dc.contributor.authorNapimoga, M. H.
dc.contributor.institutionUniv Uberaba
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal do ABC (UFABC)
dc.contributor.institutionSao Leopoldo Mandic Inst
dc.contributor.institutionRes Ctr
dc.date.accessioned2014-05-20T13:12:13Z
dc.date.available2014-05-20T13:12:13Z
dc.date.issued2011-02-01
dc.description.abstractBACKGROUND and PURPOSEThe PPAR-gamma agonist 15d-PGJ(2) is a potent anti-inflammatory agent but only at high doses. To improve the efficiency of 15d-PGJ(2), we used poly(D,L-lactide-co-glycolide) nanocapsules to encapsulate it, and function as a drug carrier system. The effects of these loaded nanocapsules (15d-PGJ(2)-NC) on inflammation induced by different stimuli were compared with those of free 15d-PGJ(2).EXPERIMENTAL APPROACHMice were pretreated (s.c.) with either 15d-PGJ(2)-NC or unloaded 15d-PGJ(2) (3, 10 or 30 mu g center dot kg-1), before induction of an inflammatory response by i.p. injection of either endotoxin (LPS), carrageenan (Cg) or mBSA (immune response).KEY RESULTSThe 15d-PGJ(2)-NC complex did not display changes in physico-chemical parameters or drug association efficiency over time, and was stable for up to 60 days of storage. Neutrophil migration induced by i.p. administration of LPS, Cg or mBSA was inhibited by 15d-PGJ(2)-NC, but not by unloaded 15d-PGJ(2). In the Cg model, 15d-PGJ(2)-NC markedly inhibited serum levels of the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IL-12p70. Importantly, 15d-PGJ(2)-NC released high amounts of 15d-PGJ(2), reaching a peak between 2 and 8 h after administration. 15d-PGJ(2) was detected in mouse serum after 24 h, indicating sustained release from the carrier. When the same concentration of unloaded 15d-PGJ(2) was administered, only small amounts of 15d-PGJ(2) were found in the serum after a few hours.CONCLUSIONS and IMPLICATIONSThe present findings clearly indicate the potential of the novel anti-inflammatory 15d-PGJ(2) carrier formulation, administered systemically. The formulation enables the use of a much smaller drug dose, and is significantly more effective compared with unloaded 15d-PGJ(2).en
dc.description.affiliationUniv Uberaba, Lab Biopathol & Mol Biol, BR-38055500 Uberaba, MG, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Biochem, Campinas, Brazil
dc.description.affiliationSão Paulo State Univ, Dept Environm Engn, Sorocaba, Brazil
dc.description.affiliationFed Univ ABC, Ctr Human & Nat Sci, Santo Andre, Brazil
dc.description.affiliationSao Leopoldo Mandic Inst, Lab Immunol & Mol Biol, Campinas, Brazil
dc.description.affiliationRes Ctr, Campinas, Brazil
dc.description.affiliationUnespSão Paulo State Univ, Dept Environm Engn, Sorocaba, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação para o Desenvolvimento da UNESP (FUNDUNESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdFAPEMIG: PPM 097/09
dc.format.extent623-632
dc.identifierhttp://dx.doi.org/10.1111/j.1476-5381.2010.01057.x
dc.identifier.citationBritish Journal of Pharmacology. Malden: Wiley-blackwell, v. 162, n. 3, p. 623-632, 2011.
dc.identifier.doi10.1111/j.1476-5381.2010.01057.x
dc.identifier.issn0007-1188
dc.identifier.urihttp://hdl.handle.net/11449/211
dc.identifier.wosWOS:000286055300007
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal of Pharmacology
dc.relation.ispartofjcr6.810
dc.relation.ispartofsjr2,603
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subject15d-PGJ(2)en
dc.subjectnanocapsulesen
dc.subjectPLGAen
dc.subjectinflammationen
dc.subjectPPAR-gammaen
dc.titleEffects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammationen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-815640.html
dcterms.rightsHolderWiley-blackwell
unesp.author.orcid0000-0003-4472-365X[5]
unesp.author.orcid0000-0002-9289-4229[4]
unesp.author.orcid0000-0003-0765-4421[2]
unesp.author.orcid0000-0002-2827-2038[3]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Ciência e Tecnologia, Sorocabapt

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Artigos - Engenharia Ambiental - Sorocaba