Synthesis and Properties of Self-assembling Paclitaxel Prodrug

Two amphiphilic prodrugs, mPEG-APA-PTX and mPEG-HDI-PTX, were prepared by conjugating PEG monomethyl ether (mPEG) short chains to paclitaxel(PTX) via p-aminophenylacetic (APA) or hexamethylene diisocyanate (HDI) as linkers. The capability of self-assembling, the PTX release kine-tics, the cytotoxicity and the life-time in plasma of them were characterized. Results showed that the prodrugs self-assembled into stable nanoparticles in aqueous solution with high drug loading content (28%). MPEG-HDI-PTX nanoparticles stayed stable in aqueous solution, but completely lost their cytotoxicity and were eliminated rapidly in plasma. While mPEG-APA-PTX nanoparticles released PTX slowly when pH=7.4, their cytotoxicity was similar to Taxol and the nanoparticles had a remarkable longer blood circulation time than Taxol. In summary, the mPEG-APA-PTX was capable of self-assembly into high drug-loaded and long plasma circulating polymeric nanoparticles.