pH响应型六臂星形共聚物的制备及药物控释研究

Synthesis of pH-responsive Six-arm Star Copolymers for Controlled Drug Delivery

通过开环聚合(ROP)和原子转移自由基聚合(ATRP)设计合成了两种两亲性六臂星形共聚物聚己内酯-b-聚甲基丙烯酸羟基乙酯(6sPCL-b-PHMEA)和聚己内酯-b-聚甲基丙烯酸二乙基氨基乙酯-b-聚甲基丙烯酸羟基乙酯(6s PCL-b-PDEAM-b-PHEMA)。采用傅立叶变换红外光谱(FT-IR)和动态光散射技术(DLS)研究了共聚物的结构和胶束的粒径,并以阿霉素(DOX)为模型药物考察了两种胶束的药物控释动力学。结果表明:两种胶束均具有合适的粒径,可作为DOX载体,6sPCL-b-PHEMA和6s PCL-b-PDEAM-b-PHEMA胶束的载药量分别为11.56%和14.23%。体外释药实验结果表明,与二嵌段星形共聚物相比,三嵌段星形共聚物具有显著的p H敏感性,pH值从7.4降至2.2时,胶束中DOX的累积释药率显著增大。这种p H响应的六臂星形共聚物具有潜在的抗癌药物控释应用前景。

Two amphiphilic six-arm star copolymers poly(ε-caprolactone)-b-poly(hydroxyethyl methacrylate)(6sPCL-b-PHMEA)and poly(ε-caprolactone)-b-poly(diethylaminoethyl methacrylate)-b-poly(hydroxyethyl methacrylate(6sPCL-b-PDEAM-b-PHEMA)with pH-responsive were designed and synthesized by ring-opening polymerization(ROP)and atom transfer radical polymerization(ATRP)process.The structure of the copolymers and the particle size of macromolecular micelles were investigated by Fourier transform infrared spectroscopy(FT-IR)and dynamic light scattering(DLS),and the drug delivery capacities of the two micelles were detected using adriamycin(DOX)as the model drug.The results showed that,the both micelles had appropriate particle size and could be used for DOX carrier,the DLC of 6sPCL-b-PHEMA and 6sPCL-b-PDEAM-b-PHEMA micelles were 11.56%and 14.23%,respectively.The release process showed that,comparing to the diblock star copolymer,triblock star copolymer had more significant pH-sensitivity.The release of DOX from micelles was enhanced with the pH decreased from 7.4 to 2.2.The pH-sensitive six-arm star copolymer might possess potential application for anticancer drug delivery.