Optimization of ligand presentation for immunoadsorption using star-configured polyethylene glycols

Medical, pharmaceutical, and industrial applications of immunoadsorption ar e frequently limited by the technologic problems of low affinity, inadequat e capacity, hydrophobicity, and bioincompatibility. To overcome these diffi culties we studied the use of star-burst configured polyethylene glycols (s tar-PEGs) with immunoreactive molecules covalently bound to the end of each of the multiple flexible arms. The optimum pH ranges were determined to ma intain stability of the tresyl chloride modified star reagents, and the che mistry was designed for their subsequent linkage to the immunoadsorbent moi ety. We then devised the chemical reactions using nitration or hydrazine ac tivation to tether these 64-arm structures to polymer supports made of poly sulfone or polymethylmethacrylate, respectively. Transmission, scanning, an d atomic force microscopy confirmed the preservation of the star configurat ion, even after linkage to the luminal surface of hollow fiber devices. To establish that these modified devices also maintained immunoadsorption reac tivity, we used a model having relevance for human autoimmune disease and d emonstrated the clearance of antihistone antibodies by tethered histones. T his novel approach to increasing the capacity of immunoadsorption benefits fr om the star configuration which provides a high density of ligand, impro ved hydrophilicity of the surface, spacing of reactive molecules away from the support structure, and possible optimization of epitope immunoreactivit y by arm-to-arm interaction of the bound molecules. (C) 2000 John Wiley & S ons, Inc. J Biomed Mater Res, 51, 29-36, 2000.