Wen-Jin An, Zhuo Lei, Xiao-Yong Yu, Chu-Han Liu, Chen Zhang, Yong Chen, Yu Liu
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引用次数: 0
Abstract
Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy-phenyl-pyridinium-modified γ-cyclodextrin (PyA-γ-CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (Kobs) between PyA-γ-CD and heparin as high as 9.85 × 106 M-1. The activated partial thromboplastin time (aPTT) experiment in porcine plasma indicates that PyA-γ-CD not only exhibits nearly complete neutralization activity for unfractionated heparin (UFH), but more importantly, it also effectively neutralizes three LMWHs (dalteparin (Dalte), enoxaparin (Enoxa), and nadroparin (Nadro)) with a broader therapeutic window compared to protamine. The top neutralization activity of PyA-γ-CD for UFH, Dalte, Enoxa, and Nadro is 94%, 91%, 99%, and 85%, respectively. Interestingly, in vivo assays in mice further suggest that PyA-γ-CD significantly reverses the severe bleeding caused by heparin overdose while exhibiting remarkable biocompatibility. Therefore, PyA-γ-CD holds significant potential as a heparin antidote for clinical applications.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.