Research On The Amphiphilic Polymers Using For The Preparation Of Drug-Loaded Micelles By Supercritical Technology

Paclitaxel is a significant antitumor drug and has been proved for its significant effect towards many kinds of cancer diseases. However, the poor water solubility of paclitaxel greatly limits its widespread application in clinical application. The amphiphilic block copolymeric micelle system is a promising method to improve paclitaxel's water solubility. Solvent evaporation method is one of the traditional processes to prepare drug-loaded micelles. However, the residual organic solvents might cause serious side effects. In view of defects of the present drug-loading amphiphilic block polymer micelle preparation technology, we developed the preparation method based on supercritical carbon dioxide. In this paper, we systematically studied the synthesis of amphiphilic block polymers. Then, the phase behavior of polyvinyl acetate in supercritical carbon dioxide has been obtained. Finally, the preparation of micelles and their characterization have been discussed in this manuscript.In this paper, three chain transfer agents were synthesized and their structures were confirmed by FTIR and 1HNMR analysis. The chain transfer agent, (S)-2-(Ethylisobutyrate)-(O-ethyl xanthate), which was prepared from potassium hydroxide, carbon disulfide and 2-bromopropanoic acid ether ester has been proved that it was beneficial to the non-conjugated monomers. And the PVAc was successfully prepared.After that, the procedure for polymerization of PVAc was discussed in this paper. The effects of reaction temperature, reaction time and the ratio of chain transfer agent to initiator for the polymerization of vinyl acetate were discussed respectively. The phase behavior of PVAc with different molecular weight in carbon dioxide at different temperature was investigated. It indicated that the low molecular weight of polyvinyl acetate has anomalously high solubility in supercritical carbon dioxide.Finally, PVAc-b-PEGMA copolymers were prepared by the RAFT polymerization of PEGMA using PVAc as macro-CTA. Then the drug-loaded micelles were prepared by solvent evaporation method and supercritical carbon dioxide evaporation method. The critical micelle concentration (CMC) of amphiphilic block polymer was 33.88 mg/L, which was determined by fluorescence probe technique. The drug-loaded micelles exhibit a narrow size distribution and relatively regular spherical shape in TEM images. Particle size distributions were investigated by dynamic light scattering (DLS), and the micelle which was prepared by supercritical carbon dioxide evaporation method has bigger size. The mean size was 476 nm. The drug loading and encapsulation efficiency of the micelle were calculated. It indicated that the micelle which prepared by supercritical carbon dioxide evaporation method has higher loading and encapsulation efficiency, and the loading capacity and encapsulation efficiency were 12.7% and 38.1%. All of the above results stated that the micelle which was prepared by supercritical carbon dioxide evaporation method exhibited better property, which indicated that the method has a promising prospect.