Delivery of Neurotherapeutics Across the Blood Brain Barrier in Stroke

Xiaoming      Hu; Meijuan      Zhang; Rehana      K Leak; Yu      Gan; Peiying      Li; Yanqin      Gao; Jun      Chen

doi:10.2174/138161212802002715

Abstract

Stroke is a devastating disease with few therapeutic options. Despite our growing understanding of the critical mechanistic events in post-stroke brain injury, the clinical translation of these findings has been less effective. A monumental hurdle to the field has been the inability of many systemically applied therapies to efficiently cross the blood brain barrier (BBB) and enter brain cells. Over the last two decades, however, significant technological achievements have overcome this obstacle to facilitate central nervous system (CNS) drug delivery. Noninvasive drug carriers, especially cell penetrating peptide (CPP) show great potential to deliver neurotherapeutics across the BBB for the treatment of ischemic brain injury. This review begins with a brief introduction to the BBB in relation to drug delivery and then provides an overview of the development of drug carriers for neurotherapeutics, with a focus on CPP-mediated transduction. We discuss recent advances and limitations in this field, as well as mechanisms underlying CPP-mediated brain targeting. We also summarize the application of CPPs in stroke research. Continuing modifications and improvements of CPPs are expected to enhance both their feasibility in clinical stroke management and their specificity towards particular cell types.

Keywords: Cell penetrating peptide, TAT protein transduction domains, blood brain barrier, stroke, neuroprotection, brain cells, central nervous system (CNS), drug delivery, neurotherapeutics, ischemic brain injury.