Synthesis of Novel Biodegradable Thermoresponsive Triblock Copolymers Based on Poly[(<i>R</i>)-3-hydroxybutyrate] and Poly(<i>N</i>-isopropylacrylamide) and Their Formation of Thermoresponsive Micelles

Abstract

Novel thermoresponsive amphiphilic triblock copolymers with two hydrophilic poly(N-isopropylacrylamide) blocks flanking a central hydrophobic poly[(R)-3-hydroxybutyrate] block were synthesized by atom transfer radical polymerization. The copolymers were characterized by gel permeation chromatography (GPC) and 1H and 13C NMR spectroscopy. The thermal stability of the copolymer was investigated by thermogravimetric analysis (TGA), and crystallization behavior was studied by differential scanning calorimetry (DSC). The water-soluble copolymers formed core−corona-type micelle aggregates in water. The critical micelle concentrations of the triblock copolymers were in the range of 1.5 to 41.1 mg/L, and the partition coefficients were in the range of (1.64−20.42) × 105. Transmission electron microscopy showed that the self-assembled micelle aggregates had well-defined spherical shape. The temperature sensitivity of the micelles was demonstrated by the phase transition of a 0.5 mg/mL aqueous polymer solution at the lower critical solution temperature (LCST). Preliminary cytotoxicity studies showed that these micelles were nontoxic and could be potential candidates for the encapsulation and release of therapeutic drugs in the biological system