PMID- 35890396
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221014
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 14
IP  - 7
DP  - 2022 Jul 20
TI  - Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of 
      the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.
LID - 10.3390/pharmaceutics14071501 [doi]
LID - 1501
AB  - Ischemic stroke is a primary origin of morbidity and mortality in the United 
      States and around the world. Indeed, several research projects have attempted to 
      discover new drugs or repurpose existing therapeutics to advance stroke 
      pharmacotherapy. Many of these preclinical stroke studies have reported positive 
      results for neuroprotective agents; however, only one compound (3K3A-activated 
      protein C (3K3A-APC)) has advanced to Phase III clinical trial evaluation. One 
      reason for these many failures is the lack of consideration of transport 
      mechanisms at the blood-brain barrier (BBB) and neurovascular unit (NVU). These 
      endogenous transport processes function as a "gateway" that is a primary 
      determinant of efficacious brain concentrations for centrally acting drugs. 
      Despite the knowledge that some neuroprotective agents (i.e., statins and 
      memantine) are substrates for these endogenous BBB transporters, preclinical 
      stroke studies have largely ignored the role of transporters in CNS drug 
      disposition. Here, we review the current knowledge on specific BBB transporters 
      that either limit drug uptake into the brain (i.e., ATP-binding cassette (ABC) 
      transporters) or can be targeted for optimized drug delivery (i.e., solute 
      carrier (SLC) transporters). Additionally, we highlight the current knowledge on 
      transporter expression in astrocytes, microglia, pericytes, and neurons with an 
      emphasis on transport mechanisms in these cell types that can influence drug 
      distribution within the brain.
FAU - Ronaldson, Patrick T
AU  - Ronaldson PT
AD  - Department of Pharmacology, College of Medicine, University of Arizona, Tucson, 
      AZ 85724-5050, USA.
FAU - Davis, Thomas P
AU  - Davis TP
AUID- ORCID: 0000-0001-8465-4973
AD  - Department of Pharmacology, College of Medicine, University of Arizona, Tucson, 
      AZ 85724-5050, USA.
LA  - eng
GR  - R01 DA051812/DA/NIDA NIH HHS/United States
GR  - R01 NS084941/NS/NINDS NIH HHS/United States
GR  - 19TPA34910113/American Heart Association/
PT  - Journal Article
PT  - Review
DEP - 20220720
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9324459
OTO - NOTNLM
OT  - ATP-binding cassette transporters
OT  - SLC transporters
OT  - blood-brain barrier
OT  - drug delivery
OT  - ischemic stroke
COIS- The authors do not have any conflict to declare.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/20
CRDT- 2022/07/27 01:39
PHST- 2022/06/06 00:00 [received]
PHST- 2022/07/13 00:00 [revised]
PHST- 2022/07/15 00:00 [accepted]
PHST- 2022/07/27 01:39 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/20 00:00 [pmc-release]
AID - pharmaceutics14071501 [pii]
AID - pharmaceutics-14-01501 [pii]
AID - 10.3390/pharmaceutics14071501 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Jul 20;14(7):1501. doi: 10.3390/pharmaceutics14071501.