Transendothelial Transport and Its Role in Therapeutics

Abstract

Present review paper highlights role of BBB in endothelial transport of various substances into the brain. More specifically, permeability functions of BBB in transendothelial transport of various substances such as metabolic fuels, ethanol, amino acids, proteins, peptides, lipids, vitamins, neurotransmitters, monocarbxylic acids, gases, water, and minerals in the peripheral circulation and into the brain have been widely explained. In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. Both diffusion and carrier mediated transport mechanisms which facilitate molecular trafficking through transcellular route to maintain influx and outflux of important nutrients and metabolic substances are elucidated. Present review paper aims to emphasize role of important transport systems with their recent advancements in CNS protection mainly for providing a rapid clinical aid to patients. This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients.

Leaky brain in neurological and psychiatric disorders: Drivers and consequences

“…The TJs and AJs restrict the paracellular transport of polar substances, including hexose sugars, amino acids, nucleosides, monocarboxylic acids and vitamins (Grammas et al, 2011; Mokgokong et al, 2014). In addition, a plethora of specialized pumps and receptor transporters facilitate and regulate the entry, endocytosis and transendothelial transport of amino acids, nutrients and certain proteins such as insulin, leptin, transferrin and insulin-like growth factors, from the peripheral circulation into the brain (Abbott et al, 2010; Lajoie and Shusta, 2015; Meng and Takeichi, 2009; Ueno et al, 2010; Upadhyay, 2014).…”

Magnetic Resonance Methods for Focused Ultrasound-Induced Blood-Brain Barrier Opening

“…Neurovascular coupling not only controls blood flow-hence modulating oxygen levels-but it also has some direct neurometabolic effects; for instance, following the neuronal glucose depletion, the permeability of the BBB for glucose is enhanced by the stimulation of the glucose transporter 1 (GLUT 1) [97]. The BBB is also responsible for controlling the transport of other substances necessary for neuronal physiology, including other energy substrates (such as lactate, acetate, ketone bodies), neurotransmitter pre-cursors, and ions [98]. The neurovascular and neurometabolic coupling is, therefore, likely to have a direct effect on the permeability of BBB with respect to all these substances.…”

Conductive Polymer‐Based Bioelectronic Platforms toward Sustainable and Biointegrated Devices: A Journey from Skin to Brain across Human Body Interfaces

“…[404] On the other hand, the integration of sensing and stimulation into cardiac drug delivery systems faces the challenges to develop platforms able to comply with the physiology providing an additional diagnostic tool for both in vitro and in vivo applications, avoiding risks of arrhythmia and preserving the native electrical pathway. [451] Along this line, electrospun nanofibers of gelatin-oligoaniline/poly(vinyl alcohol) platform have proved to enhance the adhesion and proliferation of MSCs cells while also granting on demand drug release of Dex upon electrical stimulation (Figure 11c). [403] Moreover, Dvir et al exploiting the redox activity of a PPy film developed a 3D hybrid nanocomposite scaffold for the controlled released of Dex and simultaneous monitoring of extracellular AP of CMs, capable to record regularly spaced spikes (frequency of ≈1-2 Hz) with shape and width consistent with cardiomyocyte extracellular signals (Figure 11d).…”