A Sulfonated Diblock Copolymer Exhibits Reversible Antiplatelet Activity and Enables Aqueous Dipyridamole Formulation

Abstract

Sulfonated block copolymers modulate biological function via charge-charge interactions. We report a sulfonated diblock copolymer - poly(sodium styrene sulfonate)-poly(sodium acrylamido undecanoate) (PSSNa₃₈-b-PAaU₁₀) with intrinsic charge-mediated platelet inhibition, and externally triggered reversibility, which also stabilizes poorly water-soluble dipyridamole in aqueous media. The amphiphilic architecture facilitated complete encapsulation at 5 wt% loading through block segregation and hydrophobic domain formation. Screening identified PSSNa₃₈-b-PAaU₁₀ as the most potent inhibitor of platelet aggregation in vitro, with activity mainly mediated by the sulfonated block rather than the small molecule. Inhibition persisted under static and flow conditions, confirmed by scanning electron microscopy and lactate dehydrogenase release assay, without evidence of acute cytotoxicity. Polymer-mediated effects were attenuated via polyelectrolyte complexation with a cationic heparin-binding copolymer, enabling reversible regulation of platelet function without directly neutralizing dipyridamole. Ex vivo analyses performed after intravenous administration confirmed antiplatelet efficacy. These findings establish PSSNa₃₈-b-PAaU₁₀ as a diblock copolymer with intrinsic and reversibly controlled antiplatelet activity that also supports aqueous dipyridamole formulation, providing a basis for responsive antithrombotic systems.