还原响应性聚氨酯三嵌段共聚物的合成及应用

Synthesis and Application of Redox-Responsive Polyurethane Triblock Copolymer

设计合成了一类对还原性微环境具有响应性的两亲性聚氨酯三嵌段共聚物−聚乙二醇-聚氨基甲酸酯-聚乙二醇(PEG-PU(SS)-PEG),其中PU(SS)中间嵌段由双(2-羟乙基)二硫化物和六亚甲基二异氰酸酯(HDI)经逐步聚合得到。该聚合物可以在水溶液中经纳米闪沉法自组装形成直径约100 nm、分别由PEG嵌段和PU(SS)嵌段构成壳层和内核的纳米胶束,在其疏水内核中可以负载疏水性化疗药物姜黄素,构成还原环境响应性纳米载药体系,载药量和载药效率分别可达22.2%和71.3%。体外药物释放实验结果表明:由于共聚物链上疏水性PU(SS)嵌段中二硫键结构的存在,在谷胱甘肽(GSH)作用下,可触发聚合物链发生降解,从而导致胶束结构解离,释放所负载的姜黄素;在GSH处理6 h后,姜黄素的累积释放量可达约90%。

A novel kind of redox-responsive amphiphilic polyurethane triblock copolymer,PEG-PU(SS)-PEG,was designed and synthesized,in which PEG was the hydrophilic polyethylene glycol at both ends of the copolymer chain,and the middle hydrophobic polyurethane block PU(SS)was prepared from bis(2-hydroxyethyl)disulfide and hexamethylene diisocyanate(HDI)via step-growth polymerization.PEG-PU(SS)-PEG could self-assemble into stable micelles with the average diameter of about 100 nm through nano-precipitation method in aqueous solution,in which the hydrophilic corona and the hydrophobic cores were composed of PEG and PU(SS)blocks,respectively.Hydrophobic anti-cancer drugs,such as curcumin,could be loaded into the hydrophobic micellar cores to construct redox-responsive drug nanocarriers with the drug loading content and the drug loading efficiency as high as 22.2%and 71.3%,respectively.Due to the existence of the disulfide linkages in the hydrophobic PU(SS)blocks,in the presence of glutathione(GSH),the copolymer chains could be triggered to depolymerize,resulting in the disintegration of the nano-micelles and release of loaded curcumin.After being co-incubated with GSH for 6 h,the cumulative release amount of curcumin could reach about 90%.Therefore,PEG-PU(SS)-PEG was a potential candidate for the fabrication of drug nanocarriers.