PMID- 26635971
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2059-8947 (Print)
IS  - 2059-8947 (Electronic)
VI  - 1
IP  - 1
DP  - 2015
TI  - Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino 
      Acid Transporter 2: Implications in Treating Drug Addiction.
PG  - 3-9
AB  - Chronic drug abuse is associated with elevated extracellular glutamate 
      concentration in the brain reward regions. Deficit of glutamate clearance has 
      been identified as a contributing factor that leads to enhanced glutamate 
      concentration following extended drug abuse. Importantly, normalization of 
      glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory 
      amino acid transporter 2 (EAAT2) expression has been described in several in vivo 
      studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have 
      been effective in attenuating drug-seeking and drug-consumption behavior in 
      rodent models. However, potential obstacles toward clinical translation of GLT1 
      (EAAT2) upregulators as treatment for drug addiction might include poor 
      gastrointestinal absorption, serious peripheral adverse effects, and/or 
      suboptimal CNS concentrations. Given the growing success of nanotechnology in 
      targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for 
      selective uptake across the blood brain barrier presents an ideal therapeutic 
      approach for treating drug addiction. In this review, we summarize the results 
      obtained with promising GLT1 (EAAT2) inducing compounds in animal models 
      recapitulating drug addiction. Additionally, the various nanoformulations that 
      can be employed for selectively increasing the CNS bioavailability of GLT1 
      (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) 
      induction via central delivery of drug-loaded nanoformulations is described.
FAU - Rao, Pss
AU  - Rao P
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Tennessee Health Science Center, Memphis, TN 38163, USA.
FAU - Yallapu, Murali M
AU  - Yallapu MM
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Tennessee Health Science Center, Memphis, TN 38163, USA.
FAU - Sari, Youssef
AU  - Sari Y
AD  - Department of Pharmacology and Experimental Therapeutics, University of Toledo, 
      College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA.
FAU - Fisher, Paul B
AU  - Fisher PB
AD  - Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, 
      VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, 
      Richmond, VA 23298, USA.
FAU - Kumar, Santosh
AU  - Kumar S
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, University of 
      Tennessee Health Science Center, Memphis, TN 38163, USA.
LA  - eng
GR  - R01 AA022063/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20150727
PL  - Scotland
TA  - J Pers Nanomed
JT  - Journal of personalized nanomedicine
JID - 101669268
PMC - PMC4666545
MID - NIHMS733002
OTO - NOTNLM
OT  - Drug addiction
OT  - EAAT2
OT  - Glutamate
OT  - Nanoparticles
OT  - Transcytosis
COIS- The authors declare no conflict of interest.
EDAT- 2015/12/05 06:00
MHDA- 2015/12/05 06:01
PMCR- 2015/12/01
CRDT- 2015/12/05 06:00
PHST- 2015/12/05 06:00 [entrez]
PHST- 2015/12/05 06:00 [pubmed]
PHST- 2015/12/05 06:01 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
PST - ppublish
SO  - J Pers Nanomed. 2015;1(1):3-9. Epub 2015 Jul 27.