title: Chitosan enhances the stability and targeting of immuno-nanovehicles to cerebro-vascular deposits of Alzheimer's disease amyloid protein.
abstract: Alzheimer's disease amyloid β (Aβ) proteins accumulate in the cerebral vasculature and cause cerebral amyloid angiopathy (CAA). The objective of this study was to resolve critical formulation issues in developing nanoparticles (NPs) capable of permeating the blood brain barrier (BBB) and targeting cerebrovascular Aβ proteins. To achieve this objective we designed immuno-nanovehicles, which are chitosan-coated poly lactic-co-glycolic acid (PLGA) NPs conjugated with a novel anti-Aβ antibody. Measurements made according to Derjaguin-Landau-Verwey-Overbeek (DLVO) theory indicated that the immuno-nanovehicles have a much lower propensity to aggregate than the control nanovehicles. Immuno-nanovehicles showed enhanced uptake at the BBB and better targeting of the Aβ proteins deposited in the CAA model in vitro in comparison with the control nanovehicles. In addition, chitosan enhanced aqueous dispersibility and increased the stability of immuno-nanovehicles during lyophilization, thus transforming them into ideal vehicles for delivering therapeutic and diagnostic agents to the cerebral vasculature ridden with vascular amyloid.
  
  
  BACKGROUND
  In this study, the authors report the development of chitosan-coated PLGA nanoparticles conjugated with anti-amyloid antibody to be used as immuno-nanovehicles to image cerebral amyloid angiopathy deposits in vivo. This method enables delivering therapeutic and diagnostic agents to the cerebral vasculature ridden with vascular amyloid.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Jaruszewski
authors.forename: Subramanian
authors.initials: S
authors.lastname: Ramakrishnan
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Poduslo
authors.forename: Karunya K
authors.initials: KK
authors.lastname: Kandimalla
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000175:diagnosis* / Q000276:immunology; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D000888:Antibodies, Anti-Idiotypic; D048271:Chitosan