Poly(lactic acid-glycolic acid) nanoparticles markedly improve immunological protection provided by peptide P10 against murine paracoccidioidomycosis

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dc.contributor.authorAmaral, Andre C.
dc.contributor.authorMarques, Alexandre F.
dc.contributor.authorMunoz, Julian E.
dc.contributor.authorBocca, Anamelia L.
dc.contributor.authorSimioni, Andreza R.
dc.contributor.authorTedesco, Antonio C.
dc.contributor.authorMorais, Paulo C.
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.authorTaborda, Carlos Pelleschi [UNIFESP]
dc.contributor.authorFelipe, Maria Sueli S.
dc.contributor.institutionUniversidade de Brasília (UnB)
dc.contributor.institutionUniv Catolica Brasilia
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:59:21Z
dc.date.available2016-01-24T13:59:21Z
dc.date.issued2010-03-01
dc.description.abstractBackground and purpose:The present study reports on the preparation and testing of a sustained delivery system for the immunomodulatory peptide P10 aimed at reducing the in vivo degradation of the peptide and the amount required to elicit a protective immune response against paracoccidioidomycosis.Experimental approach:BALB/c mice were infected with the yeast Paracoccidioides brasiliensis to mimic the chronic form of paracoccidioidomycosis. the animals were treated daily with sulfamethoxazole/trimethoprim alone or combined with peptide P10, either emulsified in Freund's adjuvant or entrapped in poly(lactic acid-glycolic acid) (PLGA) nanoparticles at different concentrations (1 mu g, 5 mu g, 10 mu g, 20 mu g or 40 mu g center dot 50 mu L-1). Therapeutic efficacy was assessed as fungal burden in tissues and the immune response by quantitative determination of cytokines.Key results:Animals given combined chemotherapy and P10 nanotherapy presented a marked reduction of fungal load in the lungs, compared with the non-treated animals. After 30 days of treatment, P10 entrapped within PLGA (1 mu g center dot 50 mu L-1) was more effective than 'free' P10 emulsified in Freund's adjuvant (20 mu g center dot 50 mu L-1), as an adjuvant to chemotherapy. After treatment for 90 days, the higher doses of P10 entrapped within PLGA (5 or 10 mu g center dot 50 mu L-1) were most effective. Treatment with P10 emulsified in Freund's adjuvant (20 mu g center dot 50 mu L-1) or P10 entrapped within PLGA (1 mu g center dot 50 mu L-1) were accompanied by high levels of interferon-gamma in lung.Conclusions and implications:Combination of sulfamethoxazole/trimethoprim with the P10 peptide entrapped within PLGA demonstrated increased therapeutic efficacy against paracoccidioidomycosis. P10 incorporation into PLGA nanoparticles dramatically reduced the peptide amount necessary to elicit a protective effect.en
dc.description.affiliationUniv Brasilia, Dept Biol Celular, Mol Biol Lab, Inst Biol Sci, BR-70910900 Brasilia, DF, Brazil
dc.description.affiliationUniv Brasilia, Inst Phys, BR-70910900 Brasilia, DF, Brazil
dc.description.affiliationUniv Catolica Brasilia, Brasilia, DF, Brazil
dc.description.affiliationUniv São Paulo, Inst Chem, BR-14049 Ribeirao Preto, Brazil
dc.description.affiliationUniv São Paulo, Inst Biomed Sci, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Med Mycol Lab, LIM53, MTSP, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent1126-1132
dc.identifierhttp://dx.doi.org/10.1111/j.1476-5381.2009.00617.x
dc.identifier.citationBritish Journal of Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 159, n. 5, p. 1126-1132, 2010.
dc.identifier.doi10.1111/j.1476-5381.2009.00617.x
dc.identifier.issn0007-1188
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32293
dc.identifier.wosWOS:000275402000014
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectimmunomodulatory peptideen
dc.subjectantifungal therapyen
dc.subjectbiodegradable polymersen
dc.subjectdrug deliveryen
dc.subjectnanobiotechnologyen
dc.titlePoly(lactic acid-glycolic acid) nanoparticles markedly improve immunological protection provided by peptide P10 against murine paracoccidioidomycosisen
dc.typeinfo:eu-repo/semantics/article
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