Using Bio-Layer Interferometry to Evaluate Anti-PEG Antibody-Mediated Complement Activation

  • Mostafa Mahmoud
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University Department of Pharmaceutics, Faculty of Pharmacy, Minia University
  • Elsadek Nehal E.
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University
  • Emam Sherif E.
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University
  • Ando Hidenori
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University
  • Shimizu Taro
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University
  • Abdelkader Hamdy
    Department of Pharmaceutics, Faculty of Pharmacy, Minia University Department of Pharmaceutics, Deraya University
  • Ishima Yu
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University
  • Aly Usama Farghaly
    Department of Pharmaceutics, Faculty of Pharmacy, Minia University
  • Sarhan Hatem A.
    Department of Pharmaceutics, Faculty of Pharmacy, Minia University
  • Ishida Tatsuhiro
    Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University

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説明

<p>The purpose of this study was to develop a Bio-layer interferometry (BLI) system that could be an alternative approach for the direct evaluation of anti-polyethylene glycol (PEG) immunoglobulin M (IgM)-mediated complement activation of the accelerated blood clearance (ABC) phenomenon. Complement activation is well known to play an important role in the clearance of PEGylated and non-PEGylated nanomedicines following intravenous injection. This complement system is also thought to be responsible for the ABC phenomenon wherein repeated injections of PEGylated products are bound by anti-PEG antibodies. This study used three different sources of anti-PEG antibodies: HIK-M09 monoclonal antibodies (mAbs); HIK-M11 mAbs; and antiserum containing polyclonal anti-PEG IgMs. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethylene glycol)-2000] (mPEG2000-DSPE) was immobilized as an antigen on aminopropyl silane biosensor chips of BLI. All anti-PEG IgMs in the sources increased the signals (thickness of the layer around the sensor tip) regarding binding of anti-PEG antibodies to PEG on the chips. In all anti-PEG IgM sources, further increases in the signals were observed when incubated in naïve mouse serum, which is a complement source, but not in heat inactivated (56 °C, 30 min) mouse serum, which abolishes complement activity. These findings show that the complement activation mediated via anti-PEG IgMs, which occurred on the sensor chips, was detected via BLI analysis. The complement activation induced by all anti-PEG IgM sources was confirmed via conventional enzyme-linked immunosorbent assay (ELISA), which is the conventional mode for detection of complement activation. Our study results show that BLI is a simple alternative method for the detection of complement activation.</p>

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