Targeting the blood-brain barrier for the delivery of stroke therapies

Abstract

A variety of neuroprotectants have shown promise in treating ischemic stroke, yet their delivery to the brain remains a challenge. The endothelial cells lining the blood-brain barrier (BBB) are emerging as a dynamic factor in the response to neurological injury and disease, and the endothelial-neuronal matrix coupling is fundamentally neuroprotective. In this review, we discuss approaches that target the endothelium for drug delivery both across the BBB and to the BBB as a viable strategy to facilitate neuroprotective effects, using the example of brain-derived neurotrophic factor (BDNF). We highlight the advances in cell-derived extracellular vesicles (EVs) used for CNS targeting and drug delivery. We also discuss the potential of engineered EVs as a potent strategy to deliver BDNF or other drug candidates to the ischemic brain, particularly when coupled with internal components like mitochondria that may increase cellular energetics in injured endothelial cells.

Keywords: Blood-brain barrier; Brain drug delivery; Brain-derived neurotrophic factor; Endothelial cell protection; Extracellular vesicles; Ischemic stroke; Microvesicles; Mitochondria; Nanoparticles.