Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG–TAT for drug delivery across the blood–brain barrier

Abstract Biologically active polymer core/shell nanoparticles (i.e. micelles) self-assembled from TAT–poly(ethylene glycol) (PEG)- b -cholesterol (TAT–PEG- b -Chol) were fabricated and used as carrier for targeted blood–brain barrier delivery of antibiotics. Ciprofloxacin as a model antibiotic was e...

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Bibliographic Details
Published in:Biomaterials 2008-04, Vol.29 (10), p.1509-1517
Main Authors: Liu, Lihong, Guo, Kun, Lu, Jia, Venkatraman, Subbu S, Luo, Dan, Ng, Kian Chye, Ling, Eng-Ang, Moochhala, Shabbir, Yang, Yi-Yan
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Biocompatible Materials - administration & dosage
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacokinetics
Blood-Brain Barrier - metabolism
Blood–brain barrier
Cell penetrating peptide TAT
Cells, Cultured
Cholesterol - chemistry
Core/shell nanoparticles
Dentistry
Drug Carriers
Drug delivery
Drug Delivery Systems - methods
Humans
Magnetic Resonance Spectroscopy
Microscopy, Fluorescence
Nanoparticles - administration & dosage
Nanoparticles - chemistry
PEG- b-cholesterol
Peptide Fragments - chemistry
Polyethylene Glycols - chemistry
Rats
tat Gene Products, Human Immunodeficiency Virus - chemistry
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Summary:Abstract Biologically active polymer core/shell nanoparticles (i.e. micelles) self-assembled from TAT–poly(ethylene glycol) (PEG)- b -cholesterol (TAT–PEG- b -Chol) were fabricated and used as carrier for targeted blood–brain barrier delivery of antibiotics. Ciprofloxacin as a model antibiotic was efficiently loaded into the nanoparticles by a membrane dialysis method. The actual loading level of ciprofloxacin was dependent on initial loading of ciprofloxacin and fabrication temperature. The blank and ciprofloxacin-loaded nanoparticles were characterized using dynamic light scattering and SEM. The nanoparticles were spherical in nature, having an average size lower than 200 nm. The uptake of nanoparticles with TAT by human brain endothelial cells was greater than that of the nanoparticles without TAT. Most importantly, the nanoparticles with TAT were able to cross the blood–brain barrier (BBB), and located around the cell nucleus of neurons. These nanoparticles may provide a promising carrier to deliver antibiotics across the BBB for the treatment of brain infection.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2007.11.014