Intranasal Vaccine Using P10 Peptide Complexed within Chitosan Polymeric Nanoparticles as Experimental Therapy for Paracoccidioidomycosis in Murine Model

使用 P10 肽复合壳聚糖聚合物纳米粒子的鼻内疫苗作为小鼠模型中副球孢子菌病的实验疗法

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作者:Samuel Rodrigues Dos Santos Junior, Francenya Kelley Lopes da Silva, Lucas Santos Dias, Ana Camila Oliveira Souza, Marcelo Valdemir de Araujo, Leandro Buffoni Roque da Silva, Luiz R Travassos, Andre Correa Amaral, Carlos P Taborda

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.

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