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

Anisha D'Souza, Department of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA. Electronic address: dsouzaa@duq.edu.
Kandarp M. Dave, Department of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA. Electronic address: davek1@duq.edu.
R Anne Stetler, Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: stetler@pitt.edu.
Devika S Manickam, Department of Pharmaceutical, Administrative and Social Sciences, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA. Electronic address: soundaramanickd@duq.edu.

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.