Synthesis And Characterization Of Polymeric Nanoparticles Containing Nucleoside

Polymer-drug conjugates and their nanoparticles used as drug delivery systems have attracted a lot of attentions, which could reduce side effects, prolong the circulation time in the blood, and enhance the drug accumulation in tumor cells compared with traditional small molecular drugs. In this thesis, a methodology for preparation of drug-containing polymeric micelles from chemo-enzymatic synthesized random copolymers was developed.A methodology combining enzymatic transesterifications and radical polymerization to prepare nucleoside-containing amphiphilic random polymers was developed. Through the controllable enzymatic selective transesterifications of 5-fluorocytidine. cytarabine and fluorodeoxyuridine(FUDR), the vinyl derivatives of these drugs which could be uesed as comonomers were prepared. At the same time, a series of 5-fluorocytidine-containing amphiphilic random copolymers with different 5-fluorocytidine content and the side-chain length were obtained.A series of multi-drug copolymers containing cytarabine and fluorodeoxyuridine (FUDR) were synthesized. An amphiphilic random multi-drug copolymer was prepared by radical copolymerization of FUDR and cytarabine comonomers; Amphiphilic random multi-drug copolymer with potential liver-targeting function was also synthesized by copolymerization of FUDR vinyl ester, Ara-C vinyl ester and galactose vinyl ester.The preparation of a series of drug-containing polymeric nanoparticles were achieved. A series of drug-containing polymeric nanoparticles were self-assembled from drug-containing amphiphilic homopolymers and random copolymers. And multi-drug nanoparticles were prepared by self-assembly of multi-drug copolymers containing cytarabine and fluorodeoxyuridine (FUDR).In vitro drug release behaviors and in vitro cytotoxicity of cytarabine and FUDR-containing polymeric nanoparticles were studied. The results of drug release experiments of polymeric nanoparticles showed that cytarabine and FUDR could be simultaneously released from polymeric nanoparticles, and the release behavior was correlated to pH values; In vitro cytotoxicity experiments showed that multi-drug nanoparticles containing cytarabine and FUDR could significantly inhibit the growth of HepG2 hepatoma cells.