The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.

Oxidative stress (OS) has been linked to blood–brain barrier (BBB) dysfunction which in turn has been implicated in the initiation and propagation of some neurological diseases. In this study, we profiled, for the first time, two endothelioma cell lines of mouse brain origin, commonly used as in vitro models of the blood–brain barrier, for their resistance against oxidative stress using viability measures and glutathione contents as markers. OS was induced by exposing cultured cells to varying concentrations of hydrogen peroxide and fluorescence microscopy/spectrometry was used to detect and estimate cellular glutathione contents. A colorimetric viability assay was used to determine changes in the viability of OS-exposed cells. Both the b.End5 and bEnd.3 cell lines investigated showed demonstrable content of glutathione with a statistically insignificant difference in glutathione quantity per unit cell, but with a statistically significant higher capacity for the b.End5 cell line for de novo glutathione synthesis. Furthermore, the b.End5 cells demonstrated greater oxidant buffering capacity to higher concentrations of hydrogen peroxide than the bEnd.3 cells. We concluded that mouse brain endothelial cells, derived from different types of cell lines, differ enormously in their antioxidant characteristics. We hereby recommend caution in making comparisons across BBB models utilizing distinctly different cell lines and require further prerequisites to ensure that in vitro BBB models involving these cell lines are reliable and reproducible.

The blood-brain barrier (BBB) is a robust interface between the blood and the central nervous system. Barrier type endothelium is able to limit paracellular (PC) movement, relegating molecular flux to the transendothelial pathways of brain endothelial cells (BECs). It is, therefore, apparent that any leakage via the PC shunts would effectively nullify the regulation of molecular flux across the transcellular pathways. The application of higher-resolution scanning electron microscopy (HR-SEM) illuminates the heterogenous, morphological profile that exists on the surface of BEC membranes and the relationship between these ultrastructures during the molecular construction of the PC space between adjacent BECs. In this study developing BEC monolayers were grown on mixed, cellulose esters insert membranes in a bicameral system. BEC monolayers were fixed in 2.5% glutaraldehyde, hydrated, critically dried, and sputter-coated, for imaging utilizing HR-SEM. This study, for the first time, showed membrane-bound exosomes were attached to the plasma membrane surfaces of the BECs. The exosomes were characterized as small membrane-bound, nano-sized exosomes (30–300 nm). Based on their membrane morphology and anatomical structure, exosomes appear to possess two distinct functions, namely: paracrine secretion and nanotube construction between adjacent BECs, during in vitro barrier genesis. The HR-SEM micrographs in conjunction with the Tipifarnib inhibition of exosome formation, suggests that brain capillary endothelial exosomes play a prominent role in the bilateral signaling, which contribute to the regulation of the permeability of the BBB. Given that blood-brain barrier permeability has been implicated in the progression of many neurodegenerative pathologies, the role of these exosomes and TUNTs posits the capacity of these structures to exacerbate neuropathologies that implicate BBB permeability. These findings could lead to the development of novel treatment interventions and moreover, the characterization of BBB exosomes may be a reliable target for identifying therapeutic biomarkers in neurodegenerative disease. Conversely, the presence of BBB exosomes raises a critical enterprise to target the exosome-induced nanotubes as a vehicle for transferring therapeutic treatments across the BBB.

Neural Regen Res, Official publication of Publishing House of Neural Regeneration Research China Association of Rehabilitation Medicine,China