Triblock and star-block copolymers of N-(2-hydroxypropyl)methacrylamide or N-vinyl-2-pyrrolidone and d,l-lactide: synthesis and self-assembling properties in water

Novel A-B-A triblock and star-block amphiphilic copolymers, i.e. poly(N-(2-hydroxypropyl)methacrylamide)-block-poly(d,l-lactide)-block-poly(N-(2-hydroxypropyl)metha-crylamide), poly(N-vinyl-2-pyrrolidone)-block-poly(d,l-lactide)-block-poly(N-vinyl-2-pyrrolidone), star-poly(d,l-lactide)-block-poly(N-(2-hydroxypropyl)methacrylamide) and star-poly(d,l-lactide)-block-poly(N-vinylpyrrolidone), were synthesized and characterized. These polymers were prepared by free radical polymerization of N-(2-hydroxypropyl)methacrylamide and N-vinyl-2-pyrrolidone in the presence of either poly(d,l-lactide) dithiol or star-poly(d,l-lactide) tetrakis-thiol, both biodegradable macromolecular chain-transferring agents. All copolymers self-assembled in aqueous solution to form supramolecular aggregates of 20–180 nm in size. The critical aggregation concentration of the copolymers ranged from 5 to 24 mg/L, depending on their hydrophobicity. The partition equilibrium constant of pyrene in the hydrophobic core of micelles was between 0.71×105 and 1.63×105. The triblock copolymer micelles were loaded with two model poorly water-soluble drugs, namely, indomethacin (1.5–16.4% w/w) and paclitaxel (0.4–1.5% w/w), by a dialysis procedure. These triblock and star-block copolymers could prove useful as nanocarriers for the solubilization and delivery of hydrophobic drugs.