Highly hydrophilic methacrylamide-based copolymers as precursors for polymeric nanomedicines containing anthracyclines

0580623 - ÚMCH 2025 RIV GB eng J - Článek v odborném periodiku
Pytlíková, Sára - Pechar, Michal - Chytil, Petr - Studenovský, Martin - Pola, Robert - Kotrchová, Lenka - Konefal, Rafal - Čtveráčková, Lucie - Laga, Richard - Pankrác, J. - Gao, S. - Jiang, B. - Yang, K. - Fang, J. - Filipová, Marcela - Etrych, Tomáš
Highly hydrophilic methacrylamide-based copolymers as precursors for polymeric nanomedicines containing anthracyclines.
European Polymer Journal. Roč. 205, 7 February (2024), č. článku 112756. ISSN 0014-3057. E-ISSN 1873-1945
Grant CEP: GA MŠMT LX22NPO5102; GA ČR(CZ) GA22-12483S
Grant ostatní: AV ČR(CZ) JSPS-22-01
Program: Bilaterální spolupráce
Institucionální podpora: RVO:61389013
Klíčová slova: drug delivery systems * polymer drug carriers * N‑(1,3‑dihydroxyprop-2-yl) methacrylamide
Obor OECD: Polymer science
Impakt faktor: 6, rok: 2022
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S001430572400017X?via%3Dihub

The crucial limitation of most low molecular weight cytostatic drugs, including anthracyclines, is their nonspecific biodistribution causing severe adverse effects during cancer treatment. Recently, nanomedicines such as polymer-based systems have been developed as advanced drug delivery systems. Herein, we report the design, synthesis, and characterization of highly water-soluble polymer-carriers based on N‑(1,3‑dihydroxyprop-2-yl)methacrylamide (DHPMA). Polymers differing in molecular weight, hydrodynamic size, and dispersity were synthesized via free or controlled radical polymerization and conjugated to an anthracycline drug pirarubicin (THP) via a pH-sensitive hydrazone bond achieving up to 21 wt% of THP. The DHPMA copolymers were extensively compared to the well-known drug delivery vectors, N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymers. Importantly, DHPMA-based conjugates showed excellent hydrophilicity exceeding that of HPMA-based copolymers and did not aggregate even after loading with THP reaching 21 wt%. The DHPMA-based polymer nanomedicines exhibited excellent cytotoxicity, body biodistribution, tumor accumulation, and antitumor efficacy, significantly reducing the side effects and toxicity comparable to HPMA-based systems, thus demonstrating their applicability and suitability as efficient drug carriers.
Trvalý link: https://hdl.handle.net/11104/0349466