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BRIEF RESEARCH REPORT article

Front. Drug Deliv.
Sec. CNS Drug Delivery
Volume 4 - 2024 | doi: 10.3389/fddev.2024.1433453

Induction of P-glycoprotein overexpression in brain endothelial cells as a model to study blood-brain barrier efflux transport

Provisionally accepted

The final, formatted version of the article will be published soon.

    The blood-brain barrier (BBB) is comprised of specialized brain endothelial cells (BECs) that contribute to maintaining central nervous system (CNS) homeostasis. BECs possess properties such as an array of multi-drug efflux transporters that eject various drugs and toxins, preventing their entry into the CNS. Together, it is estimated that these efflux transporters can eject up to 98% of known xenobiotic compounds. Pglycoprotein (P-gp) is a promiscuous efflux transporter at the BBB and can efflux up to 90 various substrates, representing a major hurdle in CNS drug delivery for therapeutic interventions. This necessitates the study of P-gp to discover drugs that are nonsubstrates of P-gp as well as to identify novel P-gp inhibitors. Here we report the generation of P-gp overexpressing BECs under the endogenous promoter control that could be used in the screening of P-gp substrates. These cells could provide utility in the design of drugs or identification of novel inhibitors.

    Keywords: Blood-Brain Barrier, P-Glycoprotein, efflux transport, drug screening, Brain endothelial cells, Puromycin, Drug delivery

    Received: 15 May 2024; Accepted: 10 Jun 2024.

    Copyright: © 2024 Hathcock, Knight, Tong, Meyer, Mauser, Vollmuth and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Brandon J. Kim, University of Alabama, Tuscaloosa, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.