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

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dc.contributor.author Amaral, Andre C.
dc.contributor.author Marques, Alexandre F.
dc.contributor.author Munoz, Julian E.
dc.contributor.author Bocca, Anamelia L.
dc.contributor.author Simioni, Andreza R.
dc.contributor.author Tedesco, Antonio C.
dc.contributor.author Morais, Paulo C.
dc.contributor.author Travassos, Luiz Rodolpho [UNIFESP]
dc.contributor.author Taborda, Carlos Pelleschi [UNIFESP]
dc.contributor.author Felipe, Maria Sueli S.
dc.date.accessioned 2016-01-24T13:59:21Z
dc.date.available 2016-01-24T13:59:21Z
dc.date.issued 2010-03-01
dc.identifier http://dx.doi.org/10.1111/j.1476-5381.2009.00617.x
dc.identifier.citation British Journal of Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 159, n. 5, p. 1126-1132, 2010.
dc.identifier.issn 0007-1188
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/32293
dc.description.abstract Background 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.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 1126-1132
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.relation.ispartof British Journal of Pharmacology
dc.rights Acesso aberto
dc.subject immunomodulatory peptide en
dc.subject antifungal therapy en
dc.subject biodegradable polymers en
dc.subject drug delivery en
dc.subject nanobiotechnology en
dc.title Poly(lactic acid-glycolic acid) nanoparticles markedly improve immunological protection provided by peptide P10 against murine paracoccidioidomycosis en
dc.type Artigo
dc.rights.license http://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.contributor.institution Universidade de Brasília (UnB)
dc.contributor.institution Univ Catolica Brasilia
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ Brasilia, Dept Biol Celular, Mol Biol Lab, Inst Biol Sci, BR-70910900 Brasilia, DF, Brazil
dc.description.affiliation Univ Brasilia, Inst Phys, BR-70910900 Brasilia, DF, Brazil
dc.description.affiliation Univ Catolica Brasilia, Brasilia, DF, Brazil
dc.description.affiliation Univ São Paulo, Inst Chem, BR-14049 Ribeirao Preto, Brazil
dc.description.affiliation Univ São Paulo, Inst Biomed Sci, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Med Mycol Lab, LIM53, MTSP, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.identifier.doi 10.1111/j.1476-5381.2009.00617.x
dc.description.source Web of Science
dc.identifier.wos WOS:000275402000014



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