Abstract
Novel temperature/reduction dual stimulus-responsive triblock copolymers, poly [2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate]-b-(L-polylactic acid)-SS-b-(L-polylactic acid)-b-poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol)methacrylate] [P(MEO2MA-co-OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] (SPMO), were synthesized by ring opening polymerization (ROP) of L-lactide and 2,2'-dithio diethanol (SS-DOH), and random copolymerization of MEO2MA and OEGMA monomers via atom transfer radical polymerization (ATRP) technology. The chemical structures and compositions of the novel copolymers were demonstrated by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR). The molecular weights of the novel copolymers were measured by size exclusive chromatography (SEC) and proved to have a relatively narrow molecular weight distribution coefficient (ÐM ≤ 1.50). The water solubility and transmittance of the novel copolymers were tested via visual observation and UV-Vis spectroscopy, which proved the SPMO had a good hydrophilicity and suitable low critical solution temperature (LCST). The critical micelle concentration (CMC) of the novel polymeric micelles were determined using surface tension method and fluorescent probe technology. The particle size and morphology of the novel polymeric micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The sol-gel transition behavior of the novel copolymers was studied via vial flip experiments. Finally, the hydrophobic anticancer drug doxorubicin (DOX) was used to study the in vitro release behavior of the novel drug-loaded micelles. The results show that the novel polymeric micelles are expected to become a favorable drug carrier. In addition, they exhibit reductive responsiveness to the small molecule reducing agent dithiothreitol (DTT) and temperature responsiveness with temperature changes.