结构明确的可降解醛基功能化含糖纳米微球的制备

PREPARATION OF WELL-DEFINED AND DEGRADABLE ALDEHYDE-FUNCTIONALIZED GLYCOPOLYMERIC NANOSPHERES

选择双硫代苯乙酸-1-苯基乙酯(PEPD)为RAFT试剂、以过氧化二异丙苯(DCP)为引发剂、在130℃下,茴香醚中实现了1,2:3,4-di-O-异亚丙基-6-O-(2'-甲醛-4'-苯乙烯基)-D-半乳糖(IVDG)和5,6-苯基-2-亚甲基-1,3-二氧七环(BMDO)的"活性"/可控RAFT自由基共聚合.Mn基本上随单体转化率线性增加,整个反应过程保持较窄的分子量分布(Mw/Mn～1.4),表明以上自由基共聚合体系呈现可控特征.1H-NMR的分析进一步证实了聚合物链的末端精细结构.此外,该共聚物经KOH处理后,聚合物的分子量很明显地向低分子量部分移动,且分布变宽,表明IVDG-BMDO共聚物是可以水降解的.经88%甲酸处理后,脱去保护基团,形成两亲性共聚物,该两亲性共聚物不需要外加乳化剂,在水中能够自组装形成含有大量半乳糖的、可生物降解的、醛基功能化的纳米微球.

The ＂living＂/controlled radical copolymerization of 1,2 ： 3,4-di-O-isopropylidene-6-O-（ 2＇-formyl- 4＇-vinylphenyl）-D-galactopyranose （IVDG） and 5, 6-benzo-2-methylene-1, 3-dioxepane （ BMDO ） , was successfully achieved using dicumyl peroxide （DCP） as the initiator and 1-phenylethyl phenyldithioacetate （PEPD） as the reversible addition-fragmentation chain transfer （RAFT） agent at 130℃ in anisole. The number-average molecular weight of the obtained copolymers increased in direct proportion to the monomer conversion, and the molecular weight distribution was narrow （polydispersity index 〈 1.4 ）. Various copolymers of BMDO with IVDG were synthesized by changing the molar ratio of the two monomers in the initial feed using PEPD as chain transfer reagent under RAFT reaction conditions. There was an increase in the molecular weight from 5.2× 10^3 to 1.8 × 10^4 on increasing the molar ratio of IVDG： BMDO from 20：80 to 70： 30. In general,the molecular weight of the polymers increased with increase in the amount of IVDG in the copolymers. Moreover,the copolymer composition was determined by taking the ratio of peak areas of aldehyde protons of IVDG to that of of BMDO. It is observed that the mole fraction of BMDO was less in copolymers as compared to that in the initial feed. The result was mostly because the BMDO radical is neighbor to two electron-rich oxygen atoms so as to have lower reactivity as compared to IVDG radical. The copolymer compositions and structural characterization were obtained from I H-NMR spectroscopy. Degradation behavior of these copolymers was also investigated. Removal of protective isopropylidene groups from the sugar residue in poly（BMDO-co-IVDG） was carried out quantitatively using 88% formic acid at room temperature, yielding a novel amphiphilic copolymer containing both galactopyranose and aldehyde functionalities. These amphiphilic glycopolymers self-assembled into well-defined degradable and biocompatible aldehyde-functionalized polymeric nanospheres in aqueous solutions without recourse to any surfactant. The nanospheres obtained from the resultant glycopolymer are possible to be used as nanoparticle targeted drug-delivery system.