Studies On The Preparation And Characterization Of PH-sensitive Amphiphilic Polymer

Novel amphiphilic polymers containing acid-cleavable linkages have been designed and synthesized. The kind of polymers have the potential of forming Targeted Drug Delivery System which is stable under physiological pH, but decompose easily under mildly acidic conditions. The following works were done in the thesis.(1) Amphiphilic polymer mPASA with cis-aconityl amide linker was synthesized.The mPASA was prepared through a three-step reaction with octadecyl amine, cis-aconitic anhydride and mPEG as the material. Reaction conditions includes material ratio, temperature and reaction time were studied in order to achieve a higher yield. It was found that performing the reactions at lower temperature, changing the ratio of materials and prolonging reaction time may improve the yield. However, the entire synthesis route is extremely rigorous and the overall yield was only 5 %.(2) Amphiphilic polymer GEmP with orthoester linker was synthesized. By using p-toluenesulfonic acid as the catalyst, glyceryl monostearate reacted with triethyl orthoformate to generate GE. It was found that four times of triethyl orthoformate compared with glyceryl monostearate was needed in the first reaction in order to maintain the yield of above 80%. The final product GEmP was obtained by reacting GE with mPEG. Though higher temperature is in favor of getting higher yield, the yield of GEmP is still very low. The overall yield is only 4.3%.(3) Amphiphilic polymer mPSAGSA with acetal linkers was synthesized. Using stearyl alcohol, p-hydroxybenzaldehyde, p-acetamidophenol and mPEG as the material, amphiphilic polymer mPSAGSA with acetal linkers was synthesized through a seven-step reaction. Reaction conditions includes material ratio, temperature and reaction time were studied and optimized for each step. The overall yield reached 45%.(4) Critical Micelle Concentration (CMC) and hydrolysis property of mPSAGSA was investigated.Fluorometry was used to determine the Critical Micelle Concentration (CMC) with pyrene as the fluorescent probe. The CMC value of mPSAGSA was founded to be 1.2×10-5 mol·L-1. The hydrolysis experiment showed that the mPSAGSA was quite stable in neutural phosphate buffer solutions (PBS), but can be hydrolyzed in mildly acidic PBS. A 67.4 percent of the total amount of mPSAGSA hydrolyzed in pH5.0 PBS after 22 hours. Kinetic study showed that the hydrolysis of mPSAGSA follows a first order reaction rule when the concentration of H+ was constant.