Transport Across the Blood-Brain Barrier

Abstract

The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the microenvironment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-borne neurotoxins, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. In addition to describing the unique structures of the BBB, demonstrating a variety of in vivo and in vitro experimental methods for quantification of the transport properties of the BBB, presenting the mathematical model for the paracellular pathway of the BBB, summarizing the modulation of the BBB permeability by chemical and physical stimuli, and proposing drug delivery strategies through specific trans-BBB routes, the updated chapter describes the recently developed 3D in vitro human BBB models, shows a new transcellular model for the transport of therapeutical nanoparticles across the BBB, and presents several clinical studies for systemic drug delivery by MRI (magnetic resonance imaging) guided FUS (focused ultrasound stimulation) for brain diseases.

Keywords: Blood-brain barrier (BBB); Drug delivery across the BBB; In vivo and in vitro models; Mathematical models for para- and transcellular transport; Modulation of the BBB; Permeability; Transport pathways.