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, C12‐PAGE‐PG25, were characterized by considerably larger dimensions and molar mass, reaching 78.6 nm and 253.0 × 106 g mol−1, respectively, than those of the more hydrophilic copolymer, C12‐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

Functional Polyglycidol-Based Block Copolymers for DNA Complexation

“…However, despite the introduction of a large number of densely grafted, highly hydrophilic amine hydrochloride side groups, the amphiphilicity of the C 12 -PN-PG copolymers was not lost: in aqueous solution, the formation of large (175-185 nm) aggregates was detected (Figure 2, Table 1). These aggregates were comparable or larger than the particles that the parent C 12 -PAGE-PG copolymers formed [42] and of considerably broader particle size distributions (Table 1). Furthermore, well-defined, highly contrasted, well-separated, and high electron density objects were not observed by TEM.…”

“…The copolymer precursors, abbreviated C 12 -PAGE-PG25 and C 12 -PAGE-PG60, were synthesized by sequential anionic ring-opening polymerization of allyl glycidyl ether (AGE) and ethoxyethyl glycidyl ether (protected glycidol) followed by removal of the protective ethoxyethyl groups as described elsewhere [42]. The hydrophobic hydrocarbon residue was introduced by the initiation of the polymerization with partially deprotonated dodecanol.…”

“…A stock solution of 100 µg•mL −1 salmon sperm DNA (2000 bp, M w ≈ 1.3 × 10 6 Da) was prepared in ultrapure water (>18 MΩ•cm) and used for complex formation. Well-defined amphiphilic block copolymers with pendant alkene and hydroxyl functional groups, as well as a dodecyl residue at the end of the chain (C 12 -PAGE-PG25 and C 12 -PAGE-PG60), were prepared by sequential anionic ring-opening polymerization of allylglycidyl ether (AGE) and ethoxyethyl glycidyl ether (protected glycidol) and subsequent cleavage of the protective groups as previously described [42]. The composition, molecular weights, and codes of the copolymer precursors are presented in Table 1.…”

“…The introduction of numerous hydroxyl groups enriches the possibilities for post-polymerization modification, but it is also manifested in the alteration of the properties of PG as compared to those of PEG. The hydroxyl groups were reported to promote the formation of a strongly hydrogen-bonded PG layer around hydrophobic domains of PG-based copolymers and non-phospholipid PG conjugates, which resulted in drastic changes in the aqueous solution properties and biological performance of these materials [38][39][40][41][42][43]. The present study aimed at evaluating the potential of copolymers based on linear polyglycidol to act as carriers of nucleic acids.…”

“…The present study aimed at evaluating the potential of copolymers based on linear polyglycidol to act as carriers of nucleic acids. From the library of PG-based copolymers studied earlier [38,[41][42][43], we selected diblock copolymers of polyglycidol and poly(allyl glycidyl ether) (PAGE) bearing C 12 hydrocarbon residue (hereinafter, C 12 -PAGE-PG). The PAGE moieties were modified by a thiol-ene click reaction to introduce a strong positive charge at each repeating unit.…”