Abstract
The blood brain barrier (BBB) presents a formidable challenge to the delivery of drugs into the brain. Several strategies aim to overcome this obstacle and promote efficient and specific crossing through BBB of therapeutically relevant agents. One of those strategies uses the physiological process of receptor-mediated transcytosis (RMT) to transport cargo through the brain endothelial cells toward brain parenchyma. Recent developments in our understanding of intracellular trafficking and receptor binding as well as in protein engineering and nanotechnology have potentiated the opportunities for treatment of CNS diseases using RMT. In this mini-review, the current understanding of BBB structure is discussed, and recent findings exemplifying critical advances in RMT-mediated brain drug delivery are briefly presented.
Highlights
Brain diseases are among the less understood and poorly treated conditions
Evidences indicate that claudins are essential for the formation of the para-cellular barrier and the structure is stabilized by zona occludens ZO −1, −2, and −3 and additional proteins that link the tight junctions (TJs) with the cytoskeleton (Abbott et al, 2006; Furuse, 2010)
In brain endothelial cells three types of endocytic vesicles have been identified: clathrin-coated pits involved in most of the receptor-mediated transcytosis (RMT), caveolae that participate in adsorptive-mediated endocytosis of extracellular molecules and receptor trafficking, and macropinocytotic vesicles (Mayor and Pagano, 2007)
Summary
Brain diseases are among the less understood and poorly treated conditions. In spite of the rapid growth in recent years in drug development, there is still a low success rate of effective therapies focused in diseases of the central nervous system. The isolation of the brain tissue from the peripheral circulation is thought to arise from the existence of multi-level “barriers,” established in different compartments in the central nervous system of most vertebrates (Cserr and Bundgaard, 1984; Engelhardt et al, 2017) providing protection to the neural tissue Key to those protective mechanisms is the regulation of the entry of macromolecules from the blood to the brain across the blood-brain barrier (BBB) (Abbott et al, 2006). The intimate association between neurons, glial cells, and brain microvessels in the neurovascular unit is being recognized as the functional point for regulation of cerebral blood flow.
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