Amyloid-Beta Associated with Chitosan Nano-Carrier has Favorable Immunogenicity and Permeates the BBB |
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Authors: | Zhang Songjiang Wu Lixiang |
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Institution: | (1) Department of Physiology, Xiangya Medical College, Central South University, Changsha, 410078, China;(2) Department of Physiology, Henan College of Traditional Chinese Medicine, Zhengzhou, 450000, China; |
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Abstract: | 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. |
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