Studies Of Paclitaxel Peg-Chitosan Polymer In Drug Delivery System

Amphiphilic copolymer PEG?Chitosan was designed and synthesized. This kind of copolymer may increase the solubility of hydrophobic drugs and control their release in vivo due to the formation of self-assembled micelles. It may have potential application in drug delivery system. To solve the problem of low water-solubility, harmful side-effects and enhance the therapy efficacy of paclitaxel, Polymeric micelle formed with PEG-Chitosan was prepared. Due to the numerous advantages of polymeric micelle and the biologic consistent of Chitosan, the PEG-Chitosan polymeric micelle of paclitaxel is considered to be important theoretically and practically. The following work has been done in the thesis:(1) PEG-Chitosan was synthesized through the reaction of PEG-6000 with Chitosan by two steps. Succinic anhydride was selected as the spacer to bind the two parts together in the first step. It was found that DMAP was better than pyridine. In the second step, 1-(3-dimethylaminopropyl) -3- ethyl carbodiimide (EDC·HCl) was used as dehydrating agent and N-hydroxysuccinimide (NHS) as the catalyst. HCl-Mes salt buffer solution with pH of 3-4 was proved to be the appropriate reaction medium. White powder product was finally obtained and attested to be the aim product of PEG-Chitosan by IR analysis.(2) Molecular weight and the Critical Micelle Concentration (CMC) of PEG-Chitosan were determined by viscosity measuration and fluorescence spectroscopy analysis. The size and morphology of PEG-Chitosan micelle in water were characterized by Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM), respectively. The result showed that the molecular weight was 2.14×105 and the CMC value was 2.12×10-6 mol·dm-3. The average size of the micelles was found to be 100 nm by DLS and the shape was approximately spherical by TEM examination.(3) The paclitaxel-loaded micelles were prepared by dialysis. The size and size distribution, the structure and the drug-loaded amount, the drug-fed amount were characterized by DLS, TEM and HPLC, respectively. The result showed that the average size of the paclitaxel-loaded micelles was 200 nm and was larger than that of PEG-Chitosan by DLS. The shape was changed from spherical into rod-like by TEM. It was found that as the amount of paclitaxel increased, the drug-loaded was increased step by step while the drug-fed was first increased to 95 % of the maximum and then decline by HPLC.