PMID- 27278330
OWN - NLM
STAT- MEDLINE
DCOM- 20170224
LR  - 20181202
IS  - 1521-0464 (Electronic)
IS  - 1071-7544 (Linking)
VI  - 23
IP  - 9
DP  - 2016 Nov
TI  - Brain-derived neurotrophic factor delivered to the brain using poly 
      (lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome 
      in mice with traumatic brain injury.
PG  - 3520-3528
AB  - Currently, traumatic brain injury (TBI) is the leading cause of death or 
      disabilities in young individuals worldwide. The multi-complexity of its 
      pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the 
      drug choice and delivery very challenging. The brain-derived neurotrophic factor 
      (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell 
      survival and long-term memory. However, its short half-life and low BBB 
      permeability are the main hurdles to be an effective therapeutic for TBI. Poly 
      (lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable 
      the delivery of a variety of molecules across the BBB by receptor-mediated 
      transcytosis. This study examines the ability of PLGA nanoparticles coated with 
      poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of 
      BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head 
      injuries under anesthesia. Using enzyme-linked immunosorbent assay, we 
      demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF 
      coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of 
      sham-operated mice (p < 0.001) and in both ipsi- (p < 0.001) and contralateral 
      (p < 0.001) parts of brain in TBI mice compared to controls. This study also 
      showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 h 
      post-injury prolonged the latent time in mice with TBI thereby reversing 
      cognitive deficits caused by brain trauma. Finally, neurological severity score 
      test demonstrated that our compound efficiently reduced the scores at day 7 after 
      the injury indicating the improvement of neurological deficit in animals with 
      TBI. This study shows that PLGA nanoparticles coated with PX effectively 
      delivered BDNF into the brain, and improved neurological and cognitive deficits 
      in TBI mice, thereby providing a neuroprotective effect.
FAU - Khalin, Igor
AU  - Khalin I
AD  - a Faculty of Medicine and Defence Health , National Defence University of 
      Malaysia , Kuala Lumpur , Malaysia.
FAU - Alyautdin, Renad
AU  - Alyautdin R
AD  - b Scientific Centre for Expertise of Medical Application Products , Moscow , 
      Russia.
FAU - Wong, Tin Wui
AU  - Wong TW
AD  - c iPROMISE, Non-Destructive Biomedical and Pharmaceutical Research Centre, 
      Universiti Teknologi MARA , Selangor , Malaysia.
FAU - Gnanou, Justin
AU  - Gnanou J
AD  - a Faculty of Medicine and Defence Health , National Defence University of 
      Malaysia , Kuala Lumpur , Malaysia.
FAU - Kocherga, Ganna
AU  - Kocherga G
AD  - d Ophthalmic Microsurgery Department, International Medical Center Oftalmika , 
      Kharkiv , Ukraine , and.
FAU - Kreuter, Jorg
AU  - Kreuter J
AD  - e Institute of Pharmaceutical Technology, Goethe University , Frankfurt , 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20160716
PL  - England
TA  - Drug Deliv
JT  - Drug delivery
JID - 9417471
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Surface-Active Agents)
RN  - 106392-12-5 (Poloxamer)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/metabolism
MH  - Brain/*drug effects
MH  - Brain Injuries, Traumatic/*drug therapy
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage/chemistry
MH  - Cognition/*drug effects
MH  - Half-Life
MH  - Lactic Acid/*chemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nanoparticles/administration & dosage/*chemistry
MH  - Neuroprotective Agents/administration & dosage/chemistry
MH  - Poloxamer/chemistry
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Surface-Active Agents/chemistry
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - brain-derived neurotrophic factor
OT  - drug-delivery
OT  - nanoparticles
OT  - traumatic brain injury
EDAT- 2016/06/10 06:00
MHDA- 2017/02/25 06:00
CRDT- 2016/06/10 06:00
PHST- 2016/06/10 06:00 [pubmed]
PHST- 2017/02/25 06:00 [medline]
PHST- 2016/06/10 06:00 [entrez]
AID - 10.1080/10717544.2016.1199609 [doi]
PST - ppublish
SO  - Drug Deliv. 2016 Nov;23(9):3520-3528. doi: 10.1080/10717544.2016.1199609. Epub 
      2016 Jul 16.