Functional amphiphilic block copolyethers as carriers of caffeic acid phenethyl ester

Abstract Amphiphilic diblock copolymers consisting of hydrophilic polyglycidol (PG) and hydrophobic poly(allylglycidyl ether) (PAGE) were prepared by sequential anionic ring‐opening polymerization of allylglycidyl ether and ethoxyethyl glycidyl ether followed by removal of the protective ethoxyethyl groups. The polymerization was initiated by partially deprotonated dodecanol and performed in solvent‐free conditions. The copolymers were composed of a hydrophobic dodecyl residue attached to a block of PAGE with a fixed degree of polymerization (dp = 44) and differing in length of the PG block (dp = 16 and 66, corresponding to PG contents of 25 and 60 mol%, respectively). The two copolymers were spontaneously soluble in water. Above a certain critical concentration, they formed well‐defined self‐assembled nanoparticles. Their characterization parameters were determined by static and dynamic light scattering. The aggregates of the more hydrophobic copolymer, C 12 ‐PAGE‐PG25, were characterized by considerably larger dimensions and molar mass, reaching 78.6 nm and 253.0 × 10 6 g mol −1 , respectively, than those of the more hydrophilic copolymer, C 12 ‐PAGE‐PG60. The hydrophobic moieties were proved to create a favorable environment for solubilization of caffeic acid phenethyl ester (CAPE) (the main active ingredient of propolis with cytotoxic and antioxidant activities), whereas the numerous hydroxyl groups from the PG moieties brought additional benefits related to the biocompatibility of the copolymers. Preliminary experiments with L929 fibroblast cells showed that the aggregates displayed no signs of toxicity in the applied in vitro test system, suggesting their appropriateness as a drug delivery platform. The CAPE‐loaded aggregates, however, showed dose‐dependent cytotoxic effects, indicating that CAPE retained its cytotoxic activity. © 2019 Society of Chemical Industry