Synthesis and Micellar Characterization of Novel Amphiphilic A−B−A Triblock Copolymers of N -(2-Hydroxypropyl)methacrylamide or N -Vinyl-2-pyrrolidone with Poly(ε-caprolactone)

Two novel A−B−A type amphiphilic triblock copolymers, namely poly( N -(2-hydroxypropyl)methacrylamide)- block -poly(ε-caprolactone)- block -poly( N -(2-hydroxypropyl)methacrylamide) (PHPMA- b -PCL- b -PHPMA) and poly( N -vinyl-2-pyrrolidone)- block -poly(ε-caprolactone)- block -poly( N -vinyl-2-pyrrolidone) (PVP- b -PCL- b -PVP), 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 a novel biodegradable, macromolecular chain-transferring agent, α,ω-poly(ε-caprolactone) dithiol (HS-PCL-SH). All triblock copolymers self-assembled in aqueous solutions to form supramolecular aggregates of 30−200 nm size. The critical aggregation concentration of the polymers ranged from 1 to 4 mg/L. The partition equilibrium constant ( K v ) of pyrene in the hydrophobic core of micelles was comprised between 2.5 × 10 5 and 4.2 × 10 5 . The triblock copolymer micelles were loaded by a dialysis procedure with 1−4% (w/w) of two model poorly water-soluble drugs, i.e., doxorubicin and amphotericin B. These triblock copolymers could prove useful as nanocarriers for the solubilization and transport of hydrophobic drugs. The bifunctional macromolecular chain-transferring agent reported in this work can also find application in the synthesis of a variety of novel A−B−A type biodegradable triblock copolymers.