Determination of the Accessibility of Acidic Oligosaccharide Sugar Chain to Blood-Brain Barrier Using Surface Plasmon Resonance

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  • Guo XiuLi
    Department of Pharmacology, Marine Drug & Food Institute, Ocean University of China Department of Pharmacology, School of Pharmacy, Shandong University
  • Xin XianLiang
    Department of Pharmacology, Marine Drug & Food Institute, Ocean University of China
  • Gan Li
    Department of Pharmacology, Marine Drug & Food Institute, Ocean University of China
  • Nie Qin
    Department of Pharmacology, Marine Drug & Food Institute, Ocean University of China
  • Geng MeiYu
    Department of Pharmacology, Marine Drug & Food Institute, Ocean University of China

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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.

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