Amyloid-beta associated with chitosan nano-carrier has favorable immunogenicity and permeates the BBB.
Subfragments of amyloid-beta (Abeta) 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 Abeta 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 Abeta (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 Abeta 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 Abeta. This system will further research of peptide vaccines for AD.
Songjiang
Zhang
Z
Department of Physiology, Xiangya Medical College, Central South University, Changsha 410078, China.
Lixiang
Wu
W
D023582:Alzheimer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D048271:Chitosan; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D007074:Immunoglobulin G; D048271:Chitosan