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

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.

Transcellular brain drug delivery: A review on recent advancements.

The blood-brain barrier (BBB) has a pivotal role in maintaining brain homeostasis. It robustly protects the brain parenchyma against the invasion of irrelevant substances, which may interrupt its critical function. From a pharmaceutical point of view, such a barrier may cause central nervous system (CNS) disorders refractory by restricting the therapeutics from accessing to their target sites in cerebral parenchyma. On the other side, the increasing rate of CNS disorders demands novel strategies to be developed for effective transferring the drugs through the BBB. Transcellular pathways seem to be more promising in ferrying across the BBB than paracellular route due to using the regular biological routes and retaining the BBB integrity, as well. The transcellular pathway contains several mechanisms for the transportation of therapeutic molecules, which are alternately applicable based on the physicochemical characteristics of the crossing molecule. In the present article, the most considerable transcellular routes, including the adsorptive mediated transcytosis (AMT), receptor-mediated transcytosis (RMT), cell-mediated transcytosis (CMT), and the efflux pumps-mediated drug delivery approaches were reviewed. Exosome, as a new drug carrier, utilizable in various transcellular routes, was also discussed.