Preparation Of Thermo-Sensitive Polymeric Micelles Based On Triblock Copolymer Pla-b-Pnipam-b-Pla For Drug Delivery

Using stimulus-responsive amphiphilic copolymer as drug carrier is able to improve therapeutic efficiency and reduce toxicity of drugs. As one of the most important thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM) shows intensive application prospect in biomedical field for its lower critical solution temperature (LCST) is closed to body temperature. And poly(D,L-lactide) (PLA) is one of the most interesting synthetic polymer with excellent biocompatibility and biodegradability. In this dissertation, we report our effort on the preparation of a thermosensitive amphiphilic triblock copolymer PLA-b-PNIPAM-b-PLA, which combines the thermosensitivity of PNIPAM with the biodegradability of PLA. The structure and thermosensitive property of the prepared triblock copolymer as well as its self-assemblinged micellization were investigated. The triblock copolymer was utilized as the drug carrier for controll release of anticancer adriamycin (ADR) and the influence of temperature on ADR release was examined. (1) Triblock copolymer PLA-b-PNIPAM-b-PLA was successfully synthesized by ring-opening polymerization (ROP) of D,L-lactide in the presence of dihydroxy-terminated PNIPAM (HO-PNIPAM-OH), which was obtained by radical polymerization. The structure and thermosensitive behavior of the triblock copolymer were characterized. The results obtained suggest that the PLA-b-PNIPAM-b-PLA exhibits much lower phase transition temperature than homo-PNIPAM, due to the incorporation of hydrophobic PLA segment to polymer chains. A longer PLA segment leads to a lower phase transition temperature.(2) Micellization of aqueous solution of PLA-b-PNIPAM-b-PLA was characterized by dynamic light scattering (DLS). It was found that the copolymer was able to self-assemble into spherical core-shell micelles with diameter ranging from 75 to 80 nm at 20℃. Such micelles may be used as drug carrier for passive targeting therapy of tumor. The morphology (by TEM) indicates that the PLA-b-PNIPAM-b-PLA copolymer could form core-shell micelle with multicore structure.(3)The triblock copolymer was utilized as drug carrier for the controlled released of ADR. The results suggested that the drug release systems based on triblock copolymer PLA-b-PNIPAM-b-PLA showed excellent property in loading ADR. The drug carrier system was temperature-dependent and capable of releasing the drug for a long duration.