Determination of the accessibility of acidic oligosaccharide sugar chain to blood-brain barrier using surface plasmon resonance

Abstract

There exist limitations in the detection of exogenous oligosaccharides due to their polydisperse and diversiform nature, and particularly the interference of endogenous glycosaminoglycans (GAGs). Herein, a surface plasmon resonance (SPR) assay for detecting acidic oligosaccharide sugar chain (AOSC), an anti-Alzheimer's drug candidate, in cerebrospinal fluid (CSF) was developed based on a carbohydrate antigen-antibody interaction. Rabbits were treated with AOSC intravenously and orally at 40 or 200 mg·kg-1, respectively. CSF samples were collected at given time points for quantitative determination of AOSC concentrations in the CSF using an SPR-based competitive inhibition assay, and the existence of AOSC in the CSF was indicated as a blood-brain barrier (BBB) accessibility index. AOSC concentration as low as 50 ppb (0.05 μg·ml-1) was detected in the CSF, with its peak value approaching 2.091 and 3.316 μg·ml-1 following intravenous and oral administration, respectively. This is the first time the capacity of AOSC to pass through the BBB has been confirmed using SPR-based competitive inhibition immunoassay. Importantly, the accessibility of AOSC to the BBB indicates AOSC has potential therapeutic value for treating neurodegenerative diseases, particular Alzheimer's disease. © 2006 Pharmaceutical Society of Japan.