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Poly(lactic acid‐glycolic acid) nanoparticles markedly improve immunological protection provided by peptide P10 against murine paracoccidioidomycosis
Author(s) -
Amaral André C,
Marques Alexandre F,
Muñoz Julián E,
Bocca Anamélia L,
Simioni Andreza R,
Tedesco Antonio C,
Morais Paulo C,
Travassos Luiz R,
Taborda Carlos P,
Felipe Maria Sueli S
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00617.x
Subject(s) - paracoccidioides brasiliensis , paracoccidioidomycosis , adjuvant , plga , glycolic acid , pharmacology , immune system , paracoccidioides , peptide , chemistry , microbiology and biotechnology , medicine , immunology , biology , lactic acid , biochemistry , in vitro , genetics , bacteria
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.