Synthesis, characterization and pH-Responsive self-assembly behavior of amphiphilic multiarm star triblock copolymers based on PCL, PDEAEMA, and PEG

A series of amphiphilic 4- and 6-armed star triblock copolymers based on poly( ɛ -caprolactone) (PCL), poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA), and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) were designed and synthesized by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The continuous ARGET ATRP of DEAEMA and PEGMA was in situ monitored by react infrared spectroscopy (ReactIR) and showed good first-order kinetic characteristics. The molecular weights and chemical structures of the copolymers and their precursors were confirmed by gel permeation chromatography (GPC) and 1 H NMR. The critical micelle concentration (CMC) values of the star copolymers in aqueous solution were extremely low (2.2–4.0 mg/L), depending on the architecture of the copolymers. The pH-responsive self-assembly behavior of the star copolymers in aqueous solution was investigated by a combination of dynamic light scattering (DLS), UV-vis spectrometry and scanning electron microscopy (SEM). When the pH values decreased from 10 to 3, no obvious fluctuation of the visible light transmittance of the micelle solutions was observed for lower polymer concentrations of 0.1 and 1 mg/mL, while sharp increase occurred at higher concentration of 10 mg/mL. The hydrodynamic diameters ( D h ) of the micelle solutions appeared slight increase with the increase of concentration, and increased rapidly as the pH decreased from 10 to 4 followed by a slight decrease at pH 3. The effects of pH value on the zeta potentials exhibited almost the same tendency with the D h . This may due to the fact that the protonation of tertiary amine groups in DEAEMA can induce the swelling of micelles. The PCL and PDEAEMA contents and the topological structures (4- or 6-arm) showed significant influences on the pH-sensitivity of the micelles. Overall, the results demonstrated that the structures and pH-sensitivity of these amphiphilic copolymers could be well-controlled and their self-assembled micelles are promising carriers for delivery of anticancer hydrophobic drugs.