Cyclodextrin-based molecular containers as broadspectrum in vivo sequestrants for antiplatelet drugs

Antiplatelet therapy, while essential for managing thrombotic diseases, simultaneously increases the risk of uncontrollable hemorrhage in patients during unexpected trauma or emergency surgeries. To address this severe clinical dilemma, this study introduces a conceptual shift in supramolecular medicine by repurposing traditional ‘‘drug delivery’’ vehicles into active ‘‘drug sequestrants.’’ By conjugating β-cyclodextrin (β-CD) onto a biocompatible hyaluronic acid (HA) backbone, we create a macromolecular sequestrant (HA-CD) that circulates in the bloodstream to encapsulate a broad spectrum of first-line antiplatelet agents. Leveraging the shared hydrophobic structural features of these drugs, HA-CD physically shields them through host-guest interactions, thereby rapidly restoring normal hemostasis. The polymerization design also overcomes the rapid clearance limitations of native cyclodextrins, transforming an in vitro binding concept into a safe and effective systemic in vivo intervention. Ultimately, this study demonstrates the clinical potential of utilizing a macromolecular sequestrant to rapidly manage severe bleeding complications. By successfully combining optimized systemic pharmacokinetics with broad-spectrum host-guest encapsulation, the HA-CD system offers a safe, translationally viable strategy for the functional reversal of antiplatelet agents, providing a critical safeguard for modern antiplatelet therapy.