Studies On The Polymeric Micelle As Drug Delivery System Of Paclitaxel

To solve the problem of low water-solubility, harmful side-effects and enhance the therapy efficacy of paclitaxel, Polymeric micelle formed with amphiphilic poly (ethylene glycol)-Conjugated Linoleic Acid (PEG-CLA) was prepared. Due to the numerous advantages of polymeric micelle and the anticancer activity of CLA, the PEG-CLA polymeric micelle of paclitaxel is considered to be important theoretically and practically. The following works were done in the thesis.(1) PEG-CLA was synthesized through the formation of ester bond with the carboxyl group of CLA and the hydroxyl group of PEG using p-toluenesulfonic acid and DMAP as catalyst, respectively. The influencing factors such as reactants ratio and reaction time were investigated. Finally, dicyclohexycarbodiimide (DCC) and DMAP were chose to be the coupling agent and catalyst, respectively. The ratio of the reactants was fixed to 1:1:1. The reactants and catalyst were dissolved in dichloromethane and toluene, and was stirred for 20 h under argon at room temperature. Fourier transform-infrared (FT-IR) spectroscopy measurement was used to confirm the synthesis of PEG-CLA conjugate.(2) The dialysis method was chose to prepare PEG-CLA polymeric micelles. Fluorometry was used to determine the Critical Micelle Concentration (CMC) with pyrene as the fluorescent probe. The size and size distribution of the micelles were measured by dynamic light scattering (DLS). The results showed that the CMC value of the amphiphilic polymer was 1.99×10-5 mol·L-1. The size of the micelle was approximately 100 nm and increased along with the concentration of PEG-CLA in the organic solvent. Moreover, the morphology of the micelles was investigated by transmission electron microscopy (TEM). The result shows that the particles were almost spherical in shape without aggregation.(3) The paclitaxel-loaded micelles were prepared by dialysis. The size and size distribution, the structure and the surface chemistry of micelles were characterized by DLS, TEM and X-ray photoelectron spectroscopy (XPS), respectively. The results...