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Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26
Date
2005-11-01
Author
Aktas, Y
Yemisci, M
Andrieux, K
Gursoy, RN
Alonso, MJ
Fernandez-Megia, E
Novoa-Carballal, R
Quinoa, E
Riguera, R
Sargon, MF
Celik, HH
Demir, Ayhan Sıtkı
Hincal, AA
Dalkara, T
Capan, Y
Couvreur, P
Metadata
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
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The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (SA)-biotin (BIO) technology, we describe here the design of chitosan (CS) nanospheres conjugated with poly(ethylene glycol) (PEG) bearing the OX26 monoclonal antibody whose affinity for the transferrin receptor (TfR) may trigger receptor-mediated transport across the BBB. These functionalized CS-PEG-BIO-SA/OX26 nanoparticles (NPs) were characterized for their particle size, zeta potential, drug loading capacity, and release properties. Fluorescently labeled CS-PEG-BIO-SA/OX26 nanoparticles were administered systemically to mice in order to evaluate their efficacy for brain translocation. The results showed that an important amount of nanoparticles were located in the brain, outside of the intravascular compartment. These findings, which were also confirmed by electron microscopic examination of the brain tissue indicate that this novel targeted nanoparticulate drug delivery system was able to translocate into the brain tissue after iv administration. Consequently, these novel nanoparticles are promising carriers for the transport of the anticaspase peptide Z-DEVD-FMK into the brain.
Subject Keywords
Biotechnology
,
Organic Chemistry
,
Bioengineering
,
Pharmacology
,
Pharmaceutical Science
,
Biomedical Engineering
URI
https://hdl.handle.net/11511/57045
Journal
BIOCONJUGATE CHEMISTRY
DOI
https://doi.org/10.1021/bc050217o
Collections
Department of Chemistry, Article
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
Y. Aktas et al. , “Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26,”
BIOCONJUGATE CHEMISTRY
, vol. 16, no. 6, pp. 1503–1511, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/57045.