Novel neurolisteriosis therapy using SPION as a drivable nanocarrier in gallic acid delivery to CNS.

Abstract

Neurolisteriosis is an infectious disease of the central nervous system (CNS) with a high mortality rate caused by Listeria monocytogenes. The CNS disorders suffer from inadequacy of drugs accessibility. An experimental in vivo model of neurolisteriosis was developed by oral administration of the bacteria in Wistar rats. It's speculated the capability of magnetite nanoparticles (MNPs) in ferrying gallic acid (GA), as a natural antimicrobial agent, through the blood-brain barrier (BBB) with the assistance of an external magnetic field (EMF). The capability of the formulated nanodrug in traversing through the BBB was approved by detecting blue spots in the Perls' Prussian staining of the brain tissue sections and by an increased iron content of the brain determined by the inductively coupled plasma spectroscopy. The GA release pattern and the nanodrug toxicity assay were promising. Anti-listeriosis effect of the formulated nanodrug was evaluated by molecular quantification of the relative abundance of survived bacteria in brain tissue samples. Besides, the relative expression of the listeriolysin O-encoding hly gene, the prominent virulence factor of L. monocytogenes, was determined using the rplD gene as a reference gene. The nanodrug-received rats showed a significantly less viable bacteria (13.2 ± 7.6%) and a 4.4-fold reduction in the relative expression of the hly gene in comparison to the sham group. Magnetite nanoparticles (MNPs) were synthesized by co-precipitation method, functionalized with GA, and finally coated with Tween 80. The physicochemical properties of the bare and surface modified materials were investigated using different techniques including X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopies, transmission electron microscopy (TEM), field-emission scanning electron microscopy (FESEM), dynamic light scattering (DLS) and Zeta Potential analyses, and vibrating sample magnetometry. In conclusion, MNPs displayed a considerable potential for drug delivery intentions to various target sites such as the CNS. Gallic acid exhibited a binary anti-listerial effect, the destruction of L. monocytogenes bacteria in addition to reducing the expression of the hly gene, which in turn causes reduced survivability of the bacteria in the CNS.