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

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

Autor Amaral, Andre C. Google Scholar
Marques, Alexandre F. Google Scholar
Munoz, Julian E. Google Scholar
Bocca, Anamelia L. Google Scholar
Simioni, Andreza R. Google Scholar
Tedesco, Antonio C. Google Scholar
Morais, Paulo C. Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Taborda, Carlos P. Google Scholar
Felipe, Maria Sueli S. Google Scholar
Instituição Universidade de Brasília (UnB)
Univ Catolica Brasilia
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Assunto immunomodulatory peptide
antifungal therapy
biodegradable polymers
drug delivery
nanobiotechnology
Idioma Inglês
Financiador Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Data 2010-03-01
Publicado em British Journal of Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 159, n. 5, p. 1126-1132, 2010.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Editor Wiley-Blackwell
Extensão 1126-1132
Fonte http://dx.doi.org/10.1111/j.1476-5381.2009.00617.x
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000275402000014
URI http://repositorio.unifesp.br/handle/11600/32293

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