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Review

Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?

1
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bünteweg 17, D-30559 Hannover, Germany
2
Center for Systems Neuroscience, D-30559 Hannover, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(10), 966; https://doi.org/10.3390/pharmaceutics12100966
Received: 31 August 2020 / Revised: 7 October 2020 / Accepted: 8 October 2020 / Published: 14 October 2020
(This article belongs to the Special Issue New Drug Delivery across the Blood–Brain Barrier)
The blood-brain barrier (BBB) limits the pharmacotherapy of several brain disorders. In addition to the structural and metabolic characteristics of the BBB, the ATP-driven, drug efflux transporter P-glycoprotein (Pgp) is a selective gatekeeper of the BBB; thus, it is a primary hindrance to drug delivery into the brain. Here, we review the complex regulation of Pgp expression and functional activity at the BBB with an emphasis on recent studies from our laboratory. In addition to traditional processes such as transcriptional regulation and posttranscriptional or posttranslational modification of Pgp expression and functionality, novel mechanisms such as intra- and intercellular Pgp trafficking and intracellular Pgp-mediated lysosomal sequestration in BBB endothelial cells with subsequent disposal by blood neutrophils are discussed. These intrinsic mechanisms of active drug extrusion at the BBB are potential therapeutic targets that could be used to modulate P-glycoprotein activity in the treatment of brain diseases and enhance drug delivery to the brain. View Full-Text
Keywords: P-glycoprotein; ABCB1; protein trafficking; lysosomal sequestration; extracellular vesicles; neutrophils P-glycoprotein; ABCB1; protein trafficking; lysosomal sequestration; extracellular vesicles; neutrophils
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MDPI and ACS Style

Löscher, W.; Gericke, B. Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain? Pharmaceutics 2020, 12, 966. https://doi.org/10.3390/pharmaceutics12100966

AMA Style

Löscher W, Gericke B. Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain? Pharmaceutics. 2020; 12(10):966. https://doi.org/10.3390/pharmaceutics12100966

Chicago/Turabian Style

Löscher, Wolfgang, and Birthe Gericke. 2020. "Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?" Pharmaceutics 12, no. 10: 966. https://doi.org/10.3390/pharmaceutics12100966

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