The Immune Defense against Mouse Para Coccidioidomycosis Offered by peptide p10 is significantly Enhanced by poly (Lactic Acid-Glycolic Acid) Nanoparticles

Background and goal: This study describes the development and testing of a sustained delivery method for the immunomodulatory peptide P10 with the goal of lowering the peptide's in vivo degradation and the quantity needed to trigger an immunological response that protects against Para coccidioidomycosis. Methods of the experiment: To simulate the chronic form of Para coccidioidomycosis, BALB/c mice were infected with the yeast Paracoccidioides Brasiliense’s. Every day, the animals received treatment with either sulfamethoxazole/ trimethoprim alone or in combination with peptide P10, which was either encapsulated in poly (lactic acid-glycolic acid) (PLGA) nanoparticles at varying doses (1 µg, 5 µg, 10 µg, 20 µg, or 40 µg•50 µL−1) or emulsified in Freund's adjuvant. The quantification of cytokines in the immune response and the fungal burden in tissues were used to evaluate the therapeutic efficacy. Important Findings: Animals provided when compared to the animals that were not treated, the fungal load in the lungs was significantly reduced by the combination of chemotherapy and P10 nanotherapy. Following a 30-day course of therapy, P10 encased in PLGA (1 µg•50 µL−1) demonstrated superior efficacy as an adjuvant to chemotherapy when compared to "free" P10 emulsified in Freund’s adjuvant (20 µg•50 µL−1). The highest efficacious concentrations of P10 entrapped inside PLGA (5 or 10 µg•50 µL−1) were seen after a 90-day treatment period. High levels of interferon-gamma were observed in the lung following treatment with P10 emulsified in Freund's adjuvant (20 µg•50 µL−1) or P10 entrapped within PLGA (1 µg•50 µL−1). Inferences and conclusions: The use of PLGA-encapsulated P10 peptide in conjunction with sulfamethoxazole/ trimethoprim showed improved treatment efficacy against Para coccidioidomycosis. The addition of P10 to PLGA nanoparticles significantly decreased the quantity of peptide required to produce a protective effect.