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

André C. Amaral, Alexandre F. Marques, Julián E. Muñoz, Anamélia L. Bocca, Andreza R. Simioni, Antonio C. Tedesco, Paulo C. Morais, Luiz R. Travassos, Carlos P. Taborda, Maria Sueli S. Felipe

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

36 Citas (Scopus)

Resumen

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 μg, 5 μg, 10 μg, 20 μg or 40 μg·50 μL -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 μg·50 μL -1) was more effective than 'free' P10 emulsified in Freund's adjuvant (20 μg·50 μL -1), as an adjuvant to chemotherapy. After treatment for 90 days, the higher doses of P10 entrapped within PLGA (5 or 10 μg·50 μL -1) were most effective. Treatment with P10 emulsified in Freund's adjuvant (20 μg·50 μL -1) or P10 entrapped within PLGA (1 μg·50 μL -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.

Idioma originalInglés estadounidense
Páginas (desde-hasta)1126-1132
Número de páginas7
PublicaciónBritish Journal of Pharmacology
Volumen159
N.º5
DOI
EstadoPublicada - mar 2010
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Farmacología

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