壳聚糖-O-聚(聚乙二醇甲醚甲基丙烯酸酯)接枝共聚物的ATRP合成及其自组装研究

ATRP SYNTHESIS AND SELF-ASSEMBLY BEHAVIOR OF CHITOSAN-O-PMPEGMA

以十二烷基硫酸钠-壳聚糖复合物(SCC)为起始物,将溴代异丁酸偶联到SCC的羟基上,得到溴代SCC(Br-SCC).以Br-SCC作为大分子引发剂,溴化亚铜、二联吡啶为催化剂,引发聚乙二醇单甲醚甲基丙烯酸酯(MPEGMA)原子转移自由基聚合,得到SCC-O-PMPEGMA;SCC-O-PMPEGMA中十二烷基硫酸钠(SDS)用Tris-2-甲基-2-氨基-1,3-丙二醇(Tris)解复合脱除,最终制备得到壳聚糖-O-PMPEGMA(CS-O-PMPEGMA).用FTIR和1H-NMR对中间产物与CS-O-PMPEGMA进行了表征,结果表明SCC的溴化度可以通过改变溴代异丁酸/SCC的投料比调节,改变MPEGMA/Br-SCC的投料比则可调控PMPEGMA的聚合度.用动态光散射、zeta电位仪以及TEM等手段研究了CS-O-PMPEGMA与肝素钠的复合行为,结果表明随着肝素钠/壳聚糖结构单元摩尔比(X)增加,复合胶束的粒径增大、表面电位降低;当X超过2时,肝素钠与CS-O-PMPEGMA复合形成球形纳米颗粒,其水合半径约44nm,zeta电位为-8.9mV.合成得到的CS-O-PMPEGMA具有规整化学结构,能与聚阴离子复合形成球形胶束,很有希望在基因传递与肿瘤靶向等领域得到应用.

The bromized sodium dodecyl sulfate（ SDS）-chitosan（ CS） complex（ Br-SCC） was synthesized by conjugating 2-bromo-2-methyl propionic acid to the hydroxyl groups of SCC which was used as an organo- soluble precursor in this study.Br-SCC was used as a macromolecular ATRP initiator to polymerize methyl ether poly（ethylene glycol） methacrylate （ PMPEGMA） using copper （ I） bromide /bipyridine as a catalyst,yielding SCC-O-PMPEGMA.SDS was removed from the product by precipitating SCC-O-PMPEGMA solution into aqueous tris（hydroxymethyl）amine （Tris） medium.The chemical structure of the intermediate and CS-O- PMPEGMA was studied by FTIR and 1H-NMR.The substitution degree of bromobutyric acid could be modulated by bromobutyric acid /SCC feed ratio.The degree of polymerization of PMPEGMA could be controlled by varying the PMPEGMA /Br-SCC ratio.Complexation behaviors between CS-O-PMPEGMA and heparin were studied by dynamic light scattering,zeta potential analyzer and TEM.With the increase of heparin /CS molar ratio （X）,there was an increase in the nanoparticle size and decrease in the zeta potential of the particles.When X was above 2,the size and the zeta potential reached a plateau stage.The ultimate size of the spherical nanoparticles was about 44 nm and the zeta potential was - 8.9 mV.CS-O-PMPEGMA which could be conveniently synthesized according to the scheme proposed in this study has well-defined chemical structure.The grafting of PMPEGMA has no effect on the cationic density of the final product.In addition,the copolymers could form spherical micelles with anionic agents.The above characteristics of CS-O-PMPEGMA make it promising for tumor targeting and gene delivery.