PMID- 29785179
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220123
IS  - 1616-301X (Print)
IS  - 1616-3028 (Electronic)
IS  - 1616-301X (Linking)
VI  - 28
IP  - 6
DP  - 2018 Feb 7
TI  - Nanoformulation of Brain-Derived Neurotrophic Factor with Target 
      Receptor-Triggered-Release in the Central Nervous System.
LID - 1703982 [pii]
LID - 10.1002/adfm.201703982 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is identified as a potent 
      neuroprotective and neuroregenerative agent for many neurological diseases. 
      Regrettably, its delivery to the brain is hampered by poor serum stability and 
      rapid brain clearance. Here, a novel nanoformulation is reported composed of a 
      bio-compatible polymer, poly(ethylene glycol)-b-poly(L-glutamic acid) (PEG-PLE), 
      that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF. Upon 
      simple mixture, Nano-BDNF spontaneously forms uniform spherical particles with a 
      core-shell structure. Molecular dynamics simulations suggest that binding between 
      BDNF and PEG-PLE is mediated through electrostatic coupling as well as transient 
      hydrogen bonding. The formation of Nano-BDNF complex stabilizes BDNF and protects 
      it from nonspecific binding with common proteins in the body fluid, while 
      allowing it to associate with its receptors. Following intranasal administration, 
      the nanoformulation improves BDNF delivery throughout the brain and displays a 
      more preferable regional distribution pattern than the native protein. 
      Furthermore, intranasally delivered Nano-BDNF results in superior neuroprotective 
      effects in the mouse brain with lipopolysaccharides-induced inflammation, 
      indicating promise for further evaluation of this agent for the therapy of 
      neurologic diseases.
FAU - Jiang, Yuhang
AU  - Jiang Y
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Fay, James M
AU  - Fay JM
AD  - Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, 
      University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Poon, Chi-Duen
AU  - Poon CD
AD  - Research Computer Center, University of North Carolina, Chapel Hill, NC 27599, 
      USA.
FAU - Vinod, Natasha
AU  - Vinod N
AD  - Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, 
      University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Zhao, Yuling
AU  - Zhao Y
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Bullock, Kristin
AU  - Bullock K
AD  - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, Seattle, WA 98108, USA.
FAU - Qin, Si
AU  - Qin S
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Manickam, Devika S
AU  - Manickam DS
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Yi, Xiang
AU  - Yi X
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.
FAU - Banks, William A
AU  - Banks WA
AD  - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, Seattle, WA 98108, USA.
FAU - Kabanov, Alexander V
AU  - Kabanov AV
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7362, USA.
LA  - eng
GR  - P30 CA016086/CA/NCI NIH HHS/United States
GR  - R21 NS088152/NS/NINDS NIH HHS/United States
GR  - T32 GM008570/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20171207
PL  - Germany
TA  - Adv Funct Mater
JT  - Advanced functional materials
JID - 101190390
PMC - PMC5958903
MID - NIHMS945462
OTO - NOTNLM
OT  - central nervous system
OT  - drug delivery
OT  - intranasal delivery
OT  - neurotrophic factors
OT  - polyion complexes
COIS- Conflict of Interest A.V.K. is a founder of Neuro10-9 Pharma Inc. a startup 
      company that is developing CNS therapeutics and holds patents to various 
      nanoformulations. Other authors declare no other competing financial interest, 
      except for the patent(s) filed by their institution on behalf of several 
      co-authors (A.V.K., X.Y., and Y.J.).
EDAT- 2018/05/23 06:00
MHDA- 2018/05/23 06:01
PMCR- 2019/02/07
CRDT- 2018/05/23 06:00
PHST- 2018/05/23 06:00 [entrez]
PHST- 2018/05/23 06:00 [pubmed]
PHST- 2018/05/23 06:01 [medline]
PHST- 2019/02/07 00:00 [pmc-release]
AID - 1703982 [pii]
AID - 10.1002/adfm.201703982 [doi]
PST - ppublish
SO  - Adv Funct Mater. 2018 Feb 7;28(6):1703982. doi: 10.1002/adfm.201703982. Epub 2017 
      Dec 7.