Study On Folate Targeting Pluronic/Polylactic Acid Drug Carriers

Targeted drug delivery strategies have shown great potential in solving some problems of chemotherapy such as non-selectivity and severe side effects and are able to enhance the anti-tumor efficiency of chemotherapeutic agents. In this thesis, the effects of drugs loaded in targeted polymeric nanoparticles on the treatment of cancer cells were studied, by using folate targeting polymeric nanoparticles. For the novel folate targetd polymeric nanoparticles, the active targeting interaction was achieved through the non-covalent interactions between folic acid (FA) and the folate receptor (FR).In this thesis, three kinds of folated polymers, folic acid-Pluronic-polylactic acid (FA-Pluronic-PLA), were first designed and synthesized. They are FA-F87-PLA, FA-F127-PLA and FA-P85-PLA. FA-Pluronic-PLA nanoparticles were prepared by the dialysis method. The size and morphology of nanoparticle were tested by laser light scattering and transmission electron microscopy (TEM) techniques. The results show that the morphologies of FA-F87-PLA, FA-F127-PLA and FA-P85-PLA nanoparticles are spherical micelles, and their diameters are 227nm,228nm and 160 nm, respectively.An anti-cancer drug, paclitaxel (PTX), was loaded in FA-Pluronic-PLA nanoparticles. The in vitro release behaviors of PTX-loaded FA-Pluronic-PLA nanoparticles were investigated by high-performance liquid chromatography (HPLC). It was observed that PTX-loaded FA-Pluronic-PLA nanoparticles presented an initial rapid release (up to 6 h) followed by a slow release. The total amount of PTX released was 61-92%.The in vitro targeting behaviors of FA-Pluronic-PLA nanoparticles were studied. Results from in vitro cytotoxicity studies show that PTX-loaded FA-Pluronic-PLA nanoparticles were delivered more effectively to OVCAR-3 cells under the specific interaction between the FA groups on the surface of FA-Pluronic-PLA nanoparticles and the FR on the surface of OVCAR-3 cells. The effective targeted behaviors of of FA-Pluronic-PLA nanoparticles were further comfirmed by fluorescence microscropy (FM) method.The intracellular distribution of FA-Pluronic-PLA nanoparticles was further studied by fluorescence microscropy. It was observed that FA-Pluronic-PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells.