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. From the Clinical Editor: 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.
|Original language||English (US)|
|Number of pages||11|
|Journal||Nanomedicine: Nanotechnology, Biology, and Medicine|
|State||Published - Feb 2012|
Bibliographical noteFunding Information:
The authors acknowledge the financial assistance provided by Alzheimer’s Association grant NIRG-09-133017 (KKK); NIH/NCRR/RCMI grant G12RR03020 (KKK): Neuroscience Cores for MR Studies of the Brain from NINDS grant number NS 057091 (JFP), and the Minnesota Partnership for Biotechnology and Medical Genomics (JFP). The sponsor had no role in study design, collection, data analysis, data interpretation, and played no role in the decision to submit this paper for publication.
- Blood brain barrier
- Cerebral amyloid angiopathy
- Cerebrovascular delivery
- Colloidal stability