PB0994 - Synthetic sulfonate-based block copolymers exert antiplatelet activity in rats

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Karol Depczyński

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

Co-Author(s)

AF

Aleksandra Frackiewicz

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

Co-Author(s)

JM

Joanna Miklosz

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

Kamil Kaminski

Associate Professor
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
Andrzej Mogielnicki, PhD

Associate Professor
Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
Bialystok, Podlaskie, Poland
Bartlomiej Kalaska, PhD

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

Background: Antiplatelet drugs, while effective in reducing arterial thrombosis risk, may also increase the risk of bleeding, and most of them lack effective reversal agents. Anionic block copolymers synthesized by reversible addition-fragmentation chain transfer polymerization can exhibit anticoagulant, antithrombotic, and potentially antiplatelet activity. These compounds can be reversed using an oppositely charged copolymer (Kalaska et al. Biomacromolecules 2018).

Aims: This study investigates the potential of sulfonate-based block copolymers to inhibit platelet aggregation and their neutralization using a cationic heparin-binding copolymer (HBC).

Methods: In vitro experiments were conducted using whole blood from Wistar rats. The antiplatelet effect of polymers composed of either poly(sodium styrenesulfonate) (PSSS) block and/or poly(sodium 2-acrylamido-2-methylpropanesulfonate) (PAMPS) and a neutral poly(ethylene glycol) (PEG) block, denoted as P1, P3, P6, P8, and P10, was assessed by collagen-induced platelet aggregation via impedance technique. The most active polymers, P1 and P8, were further evaluated in platelet-rich plasma (PRP) or washed platelets by collagen, thrombin, or ADP-induced optical aggregometry. The reversibility of the antiplatelet effect by HBC was also estimated. The polymers were also intravenously administered to animals, blood and PRP were then collected for collagen-induced platelet aggregation. Animal procedures were ethically approved by the Local Committee.

Results: P1 and P8 polymers concentration-dependently inhibited collagen- and thrombin-induced aggregation in vitro. P1 polymer with degrees of polymerization of PEG, PAMPS, and PSSS blocks equal to 16, 360, and 100, respectively, showed strong antiplatelet activity in vivo (Figure 1A). Additionally, we demonstrated the reversibility of the antiplatelet effects of both polymers with HBC (Figure 1B).

Conclusion(s): Our findings indicate the potential of synthetic sulfonate-based block copolymers to inhibit platelet aggregation with the ability to be neutralized by an oppositely charged copolymer. This on-demand modulation of platelet activity may improve the safety of thrombotic therapy.

Funding: Medical University of Bialystok, 2024.