Brain-targeted delivery of protein using chitosan- and RVG peptide-conjugated, pluronic-based nano-carrier

Abstract Brain-targeted delivery of drug or imaging agent is hard to achieve efficiently due to the infiltrative nature of the blood-brain barrier (BBB). Moreover, delivery of therapeutic proteins to brain tissue is further limited by the size and physic-chemical properties of proteins. In this work...

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Bibliographic Details
Published in:Biomaterials 2013-01, Vol.34 (4), p.1170-1178
Main Authors: Kim, Ja-Young, Choi, Won Il, Kim, Young Ha, Tae, Giyoong
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
BBB
beta-Galactosidase - administration & dosage
beta-Galactosidase - pharmacokinetics
Brain
Brain - metabolism
Brain - pathology
Chitosan
Chitosan - chemistry
Dentistry
Diffusion
Diseases
Drug delivery systems
Glycoproteins - pharmacokinetics
Imaging
Male
Mice
Mice, Inbred C3H
Mice, Nude
Nanocapsules - administration & dosage
Nanocapsules - chemistry
Nanostructure
Peptides
Peptides - pharmacokinetics
Pluronic
Poloxamer - pharmacokinetics
Proteins
Rabies virus
Rabies virus - chemistry
Rabies virus glycoprotein (RVG)
Tissue Distribution
β-galactosidase
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Summary:Abstract Brain-targeted delivery of drug or imaging agent is hard to achieve efficiently due to the infiltrative nature of the blood-brain barrier (BBB). Moreover, delivery of therapeutic proteins to brain tissue is further limited by the size and physic-chemical properties of proteins. In this work, we developed a chitosan-conjugated Pluronic-based nano-carrier with a specific target peptide for the brain (rabies virus glycoprotein; RVG29) and applied for the protein delivery to the brain. The in-vivo brain accumulation of the nano-carrier in mice followed i.v injection was optically monitored with Cy5.5-conjugation to the nano-carrier, and the result showed that the Pluronic-based nano-carrier conjugated with both chitosan and the peptide was very efficient for the accumulation in brain tissue and was remarkably better than the nano-carrier conjugated with the peptide only. β-galactosidase, a model protein, was also delivered and accumulated efficiently in the brain by loading in the nano-carrier, analyzed by the bio-distribution of β-galactosidase. The delivered protein in the brain also maintained its bioactivity. Therefore, RVG29- and chitosan-conjugated Pluronic-based nano-carrier could be potentially useful for the diagnosis and therapy of brain diseases.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.09.047