作者：Yueying He, Yan Zhang, Yan Xiao, Meidong Lang
关键字：Micelles, N-isopropylacrylamide, Hydrazone bond, Dual-responsive, Ketone-bearing poly(ε-caprolactone), Drug release
论文来源：期刊
发表时间：2010年

An amphiphilic copolymer was successfully synthesized by grafting aminooxy- terminated Poly(N-isopropylacrylamide) (At-PNIPAM) onto the backbone of ketone-bearing poly(ε-caprolactone) (P(OPD-co-CL) using hydroxyethyl hydrazine as space molecule and p-nitrophenyl chloroformate as coupling agent. The hydrazone bond was formed between hydroxyethyl hydrazine and ketone group of POPD segment in the copolymer. To compare with the graft copolymer, At-PNIPAM conjugated P(OPD-co-CL) block polymer was also prepared. Both graft and block copolymers underwent self-assembly to the micelles with core-shell structure and the thermo-response, which originated from the thermo-sensitivity of PNIPAM. Besides the thermo-response of graft copolymer, it also showed pH-response attributed to the broken of hydrazone bond at acidic condition. A fluorescence probe study showed the low critical micelle concentrations (CMCs, 6.7 mg/L for grafted polymer and 14.3 mg/L for block polymer) of the micelles, confirming the formation of stable micelles. Morphological investigation showed that the blank and drug-loaded micelles both had spherical and uniform shapes. The sizes of the blank and drug-loaded micelles prepared from graft polymer and block polymer were 123.5 nm, 146.5 nm, 197.5 nm and 211.5 nm, respectively. The lower critical solution temperature (LCST) for the graft polymer was 34.3 ^oC, whereas that for block polymer was 28.1 ^oC, demonstrating a thermo-response. As a drug delivery, the graft polymeric micelles exhibited the dual-response release profiles in vitro, which were confirmed by the drug release studies. The obtain results showed the thermo-triggered decelerated release at pH7.4, and the pH-triggered accelerated release at 25 ^oC, indicating the graft polymeric micelles would be a promising site-specific drug delivery for enhancing the bioavailability of the drug in targeting pathological areas.