Fabrication of star-shaped, thermo-sensitive poly(N-isopropylacrylamide)-cholic acid-poly(ɛ-caprolactone) copolymers and their self-assembled micelles as drug carriers

Novel star-shaped copolymers, comprised of a thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) segment and three hydrophobic poly(ɛ-caprolactone) (PCL) arms were fabricated. The copolymers were prepared by stannous octoate (Sn(Oct)2) catalyzed ring-opening polymerization of ɛ-caprolactone (CL) using cholic acid functionalized PNIPAAm as the macroinitiator. The lower critical solution temperatures (LCST) of the copolymer solutions are attractively close to the nominal physiologic temperature at around 37 °C. The in vitro cytotoxicity test indicated no apparent cytotoxicity. The amphiphilic star-shaped copolymers were capable of self-assembling into spherical micelles in water at room temperature, and they possessed low critical micelle concentrations (CMCs) of 3 ∼ 8 mg/L in aqueous solution determined by fluorescence spectroscopy using pyrene as a probe. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited a spherical shape with a size range of 30 ∼ 75 nm in diameter. In addition, the anticancer drug, methotrexate (MTX) can be loaded effectively in the polymeric micelles and its release was temperature-stimulated, which suggests that these materials have good potential as “intelligent” drug carriers.