Amyloid-Beta Associated with Chitosan Nano-Carrier has Favorable Immunogenicity and Permeates the BBB
- 694 Downloads
Subfragments of amyloid-beta (Aβ) appear to protect neurons from Alzheimer’s disease (AD). The permeability of the blood–brain barrier (BBB) has limited in vivo research. The aim of this study is to explore permeation of the BBB by chitosan nanoparticles loaded with Aβ and to evaluate immunogenicity of these particles. Chitosan microspheres were prepared by mechanical stirring emulsification methods combined with chemical crosslinking. Morphological characteristics of the nanoparticles were examined using high-resolution transmission electron microscopy. The peptide association efficiency was determined by high-performance liquid chromatography. Fluorescently labeled chitosan nanoparticle-intramembranous fragments of Aβ (NP-IF-A) were administered systemically to mice in order to evaluate brain translocation by fluorescence microscopy. The immunogenicity of the nano-vaccine was determined by enzyme-linked immunosorbent assay (ELISA). All nanoparticles analyzed were well-separated, roughly spherical structures with uniform particle size distribution in the range of 15.23 ± 10.97 nm. The peptide association efficiency was 78.4%. The brain uptake efficiency of nano-antigen was 80.6%; uptake efficiency of antigen alone was only 20.6%. ELISA showed that the nano-vaccine had favorable immunogenicity. A chitosan nano-carrier for Aβ allowed permeation of the BBB and was non-immunogenic. These findings indicate that this novel targeted nano-vaccine delivery system can be used as a carrier for Aβ. This system will further research of peptide vaccines for AD.
Key wordsamyloid-beta blood–brain barrier immunogenicity nanoparticle
This work was supported by the Construct Program of the Key Discipline in Hunan Province, Natural Science Foundation of Hunan Province, China (No.08JJ307), and National High Tech 863 Grant (Project No. 2007AA021901).
- 20.Kim MS, Sung MJ, Seo SB, Yoo SJ, Lim WK, Kim HM. Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid beta peptide and interleukin-1beta. Neuroscience Letters. 2002;321:105–9. doi: 10.1016/S0304-3940(02)00066-6.PubMedCrossRefGoogle Scholar
- 24.Shibata Y, Foster LA, Metzger WJ, Myrvik QN. Alveolar macrophage priming by intravenous administration of chitin particles, polymers of N-acetyl-d-glucosamine, in mice. Infect. Immunol. 1997;65:1734–41.Google Scholar