Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

Abstract

The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.

Keywords: brain barriers; brain targeting; drug delivery; extracellular vesicles; neurological disorders.

Figure 1

Schematic overview of the discussed literature on (un)modified extracellular vesicles (EVs) in this review. Unmodified EVs derived from various specific cell sources are described to possess a natural brain targeting capacity. Additionally, EVs can be engineered with diverse targeting ligands to obtain enriched brain targeting.

Figure 2

Schematic overview of the discussed practical considerations towards extracellular vesicles (EVs) as a therapeutic delivery platform to the brain.

Figure 3

Overview of the brain targeting extracellular vesicle (EV) detection methods of the summarized literature (Table 1 and Table 2). Pursuing the combination of both EV tracing and proof of functional cargo delivery will provide stronger evidence of EV brain targeting capacities.