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Intranasal Vaccine Using P10 Peptide Complexed within Chitosan Polymeric Nanoparticles as Experimental Therapy for
Samuel Rodrigues Dos Santos Junior1, Francenya Kelley Lopes da Silva2, Lucas Santos Dias1
1Departamento de Microbiologia, Instituto de Ciências Biomedicas, Universidade de Sao Paulo, Sao Paulo, SP 05508-000, Brazil.
Abstract:
Paracoccidioidomycosis (PCM) is a granulomatous fungal disease caused by the dimorphic fungal species of Paracoccidioides, which mainly affects the lungs. Modern strategies for the treatment and/or prevention of PCM are based on a Th1-type immune response, which is important for controlling the disease. One of the most studied candidates for a vaccine is the P10 peptide, derived from the 43 kDa glycoprotein of Paracoccidioides brasiliensis. In order to improve its immune modulatory effect, the P10 peptide was associated with a chitosan-conjugated nanoparticle. The nanoparticles presented 220 nm medium size, poly dispersion index (PDI) below 0.5, zeta potential of +20 mV and encapsulation efficiency around 90%. The nanoparticles' non-toxicity was verified by hemolytic test and cell viability using murine macrophages. The nanoparticles were stable and presented physicochemical characteristics desirable for biological applications, reducing the fungal load and the usual standard concentration of the peptide from 4 to 20 times.
Insights
Chitosan nanoparticles enhance the P10 peptide's immune response against Paracoccidioidomycosis (PCM). This novel formulation reduces the required peptide concentration, offering a promising strategy for PCM treatment and prevention.
Area of Science:
- Mycology
- Immunology
- Nanotechnology
Background:
- Paracoccidioidomycosis (PCM) is a significant fungal disease primarily affecting the lungs, caused by *Paracoccidioides* species.
- Effective PCM control relies on inducing a Th1-type immune response.
- The P10 peptide, derived from *Paracoccidioides brasiliensis* glycoprotein, is a key vaccine candidate.
Purpose of the Study:
- To enhance the immunomodulatory effects of the P10 peptide.
- To develop a chitosan-conjugated nanoparticle formulation for improved P10 peptide delivery.
- To evaluate the physicochemical properties, safety, and efficacy of the P10-loaded nanoparticles.
Main Methods:
- Synthesis and characterization of chitosan-conjugated nanoparticles encapsulating the P10 peptide.
- Assessment of nanoparticle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency.
- Evaluation of nanoparticle non-toxicity using hemolytic assays and murine macrophage cell viability tests.
- Determination of the efficacy in reducing fungal load and the effective concentration of the P10 peptide.
Main Results:
- The developed nanoparticles exhibited desirable physicochemical properties: 220 nm size, PDI < 0.5, zeta potential +20 mV, and ~90% encapsulation efficiency.
- Hemolytic tests and cell viability assays confirmed the non-toxicity of the nanoparticles.
- The formulation demonstrated stability and significantly reduced fungal load.
- The effective concentration of the P10 peptide was reduced by 4 to 20 times compared to the standard concentration.
Conclusions:
- Chitosan-conjugated nanoparticles provide a stable and non-toxic delivery system for the P10 peptide.
- This formulation significantly enhances the therapeutic potential of the P10 peptide in controlling PCM.
- The reduced peptide concentration required highlights the efficiency of this nanoparticle-based approach for PCM treatment and prevention.
