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Acquired and Critical Care Bleeding

PB0995 - New antiplatelet formulation based on block copolymers and dipyridamole: experimental studies in rats

Tuesday, June 25, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall

    Co-Author(s)

  • AF

    Aleksandra Frackiewicz

    PhD student
    Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
    Bialystok, Podlaskie, Poland

  • Karol Depczyński

    Student
    Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
    Białystok, Podlaskie, Poland

  • MO

    Magdalena Obloza

    PhD Student
    Faculty of Chemistry, Jagiellonian University, Krakow, Poland
    Krakow, Malopolskie, Poland

  • SY

    Shin-Ichi Yusa

    Professor
    Department of Applied Chemistry, University of Hyogo, Hyogo, Japan
    Hyogo, Hyogo, Japan

  • DP

    Dariusz Pawlak

    Professor
    Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
    Bialystok, Podlaskie, Poland

  • KS

    Krzysztof Szczubialka

    Professor
    Faculty of Chemistry, Jagiellonian University, Krakow, Poland
    Krakow, Malopolskie, Poland

  • Bartlomiej Kalaska, PhD

    Associate Professor
    Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
    Bialystok, Podlaskie, Poland

    • Presenting Author(s)

  • Andrzej Mogielnicki, PhD

    Associate Professor
    Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
    Bialystok, Podlaskie, Poland

Background: While antiplatelet drugs are widely available, the need for safer agents with reduced bleeding risks and reversible pharmacological activity persists. Sulfonate-containing block copolymers inhibit platelet aggregation (Kalaska et al. Biomacromolecules 2018), and among these, those with a hydrophobic block may also solubilize hydrophobic compounds (Mizusaki et al. Polymers 2016). We hypothesized that the solubilization of dipyridamole, an antiplatelet inhibitor of phosphodiesterase, with these polymers, could increase its solubility and synergistically amplify efficacy. Additionally, it would allow for the neutralization of the antiplatelet effect using a block copolymer with an opposite charge.

Aims: The aim of the study was to investigate the antiplatelet effects of an anionic block copolymer and dipyridamole in a novel therapeutic formulation and evaluate its reversibility using a cationic block copolymer (HBC).

Methods: The studies were performed in vitro by incubating solubilized dipyridamole with whole blood or platelet-rich plasma (PRP) and in vivo after its intravenous administration to Wistar rats. The antiplatelet activity was evaluated using ADP-induced optical aggregation in PRP and collagen-induced impedance aggregation in whole blood. Animal procedures were ethically approved by the Local Committee.

Results: Among tested anionic amphiphilic block copolymers, a polymer containing polystyrene sulfonate (PSSS) and poly(sodium11-(acrylamido)undecanoate) (PAaU) blocks exerted the strongest antiplatelet activity in vitro, therefore it was selected to solubilize dipyridamole. Both, in vitro and in vivo, solubilized dipyridamole inhibited platelet aggregation with increasing concentration or dose (Figure 1A-C). Moreover, that antiplatelet effect was reversed by HBC (Figure 1D).

Conclusion(s): We have developed a novel therapeutic formulation of dipyridamole that possesses both antiplatelet efficacy and reversibility through an antidote. This approach holds significant promise for improved control of antiplatelet therapy in patients.

Funding: Medical University of Bialystok, 2024.