Journal
BIOMATERIALS
Volume 31, Issue 5, Pages 908-915Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.09.104
Keywords
Nanoparticle; Brain targeting; Trimethylated chitosan; Neuroprotective effects; Biochemical parameters; Co-Q(10)
Funding
- National Basic Research Program of China (973 Program) [2009CB930300]
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Trimethylated chitosan (TMC) surface-modified poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (TMC/PLGA-NP) were synthesized as a drug carrier for brain delivery. TMC was covalently coupled to the surface of PLGA nanoparticles (PLGA-NP) via a carbodiimide-mediated link. The zeta potential of TMC/ PLGA-NP was about 20 mV with a mean diameter around 150 nm. 6-coumarin loaded PLGA-NP and TMC/PLGA-NP were injected into the caudal vein of mice, and fluorescent microscopy of brain sections showed a higher accumulation of TMC/PLGA-NP in the cortex, paracoele, the third ventricle and choroid plexus epithelium, while no brain uptake of PLGA-NP was observed. There was no pronounced difference in cell viability between TMC/PLGA-NP and PLGA-NP as shown by MTT assay. Behavioral testing showed that the injection of coenzyme Q(10) loaded TMC/PLGA-NP greatly improved memory impairment, restoring it to a normal level, but the efficacy was slight for loaded PLGA-NP, without TMC conjugation. The senile plaque and biochemical parameter tests confirmed the brain-targeted effects of TMC/PLGA-NP. These experiments show that TMC surface-modified nanoparticles are able to cross the blood-brain barrier and appear to be a promising brain drug delivery carrier with low toxicity. (C) 2009 Elsevier Ltd. All rights reserved.
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