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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.
- Source :
-
Drug delivery [Drug Deliv] 2016 Nov; Vol. 23 (9), pp. 3520-3528. Date of Electronic Publication: 2016 Jul 16. - Publication Year :
- 2016
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Abstract
- 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.
- Subjects :
- Animals
Blood-Brain Barrier metabolism
Brain-Derived Neurotrophic Factor chemistry
Half-Life
Male
Mice
Mice, Inbred C57BL
Nanoparticles administration & dosage
Neuroprotective Agents administration & dosage
Neuroprotective Agents chemistry
Poloxamer chemistry
Polylactic Acid-Polyglycolic Acid Copolymer
Surface-Active Agents chemistry
Brain drug effects
Brain Injuries, Traumatic drug therapy
Brain-Derived Neurotrophic Factor administration & dosage
Cognition drug effects
Lactic Acid chemistry
Nanoparticles chemistry
Polyglycolic Acid chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0464
- Volume :
- 23
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Drug delivery
- Publication Type :
- Academic Journal
- Accession number :
- 27278330
- Full Text :
- https://doi.org/10.1080/10717544.2016.1199609