Micelle-forming graft copolymers with dual drug binding Markéta Frejková 1 , Kevin Kotalík 1 , Eva Randárová 1 , Benjamin Nottelet 2 , Tomáš Etrych 1 1 Institute of Macromolecular Chemistry AS CR, Czech Republic, 2 Institut des Biomolécules Max Mousseron, Université Montpellier, France Polymeric drug delivery systems offer many advantages compared to low-molecular-weight drugs, such as reducing adverse effects and providing suitable pharmacokinetics, resulting in much more effective treatment of various diseases. 1 We synthesized biodegradable micelle-forming amphiphilic graft copolymers, prepared by grafting of N -(2-hydroxypropyl)methacrylamide based copolymers (pHPMA) to a modified poly( ε −caprolactone) (PCL). By changing the length of pHPMA, or PCL chains, we can prepare various graft copolymers with different physico-chemical properties. The system forms stable micelle-like structures in an aqueous solution, which can prolong circulation in the bloodstream and significantly improve accumulation in solid tumors. The main advantage of the designed system lies in the possibility of combining active compounds, e.g. drugs, imaging agents, or targeting molecules, on one single polymer carrier thanks to dual drug binding. In our system, the active molecules can be either covalently attached to pHPMA chains via the hydrolyzable bond and/or non- covalently entrapped within the PCL core. Non-covalent entrapment into the PCL core is highly advantageous for the hydrophobic active molecules without a suitable functional group for attachment to the polymer carrier, whose chemical modification is problematic or leads to loss of activity. The long-term biodegradation of the PCL core, the high micelle stability, the biocompatibility of the system, and the possibility to combine different types of drugs on one carrier are aspects, which make this system promising for the treatment of different types of malignancies. 2 This work was supported by the Czech Science Foundation (No. 22-12483S). References
1. K. Ulbrich et al., Chem. Rev., 2016, 116, 5338–5431. 2. M. Bláhová et al., Polym. Chem., 2020, 11, 4438–4453.
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