第三代紫杉烷靶向控释胶束的制备与性能  

Preparation and Propeties of Third-Generation Taxoid Loaded Targeted Delivery Micelles

作　　者：孙琪 李欣 龚飞荣[1] 陆冲[1] SUN Qi;LI Xin;GONG Feirong;LU Chong(Key Laboratory for Ultrafine Materials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学材料科学与工程学院,超细材料制备与应用教育部重点实验室,上海200237

出　　处：《功能高分子学报》2024年第3期223-231,共9页Journal of Functional Polymers

摘　　要：第三代紫杉烷结构中含有二氟乙烯基(DFV),该结构可显著降低紫杉烷分子和P-糖蛋白(P-gp)的结合能力,从而减少药物在肿瘤细胞内的外排。相比已上市的第一代和第二代紫杉烷药物(紫杉醇、多西他赛和卡巴他赛),第三代紫杉烷具有更强的抗多药耐药性,对肿瘤的抑制效果也更显著。为了实现第三代紫杉烷药物在肿瘤细胞内的靶向控释,合成了一种硫辛酸封端的两亲性嵌段共聚物,并利用固体分散-薄膜水化法制备了包载第三代紫杉烷的还原敏感性聚合物胶束。采用傅里叶红外光谱(FT-IR)和核磁共振氢谱(1H-NMR)验证了药物的包封情况,使用紫外光谱(UV)测定了胶束的载药量和包封率,考查了胶束的体外稳定性,并研究了载药胶束的体外释放规律、细胞毒性和体内抑瘤效果。结果表明:该胶束的粒径均一,具有良好的稳定性和还原敏感的药物控释特性,对A549肺腺癌的抑制效果显著强于紫杉醇制剂。Third-generation taxoid contains difluorovinyl(DFV)in its structure,which significantly reduces the binding ability of P-glycoprotein(P-gp)with the drug molecules,thereby reducing drug efflux from tumor cells.Compared to the marketed first-and second-generation taxoids(paclitaxel,docetaxel,and cabazitaxel),third-generation taxoid has better resistance to multidrug resistance and more significant tumor inhibition efficacy.To achieve targeted drug delivery of third-generation taxoid in tumor cells,an amphiphilic block copolymer capped with lipoic acid was synthesized and reduction-sensitive polymeric micelles encapsulating third-generation taxoid(SB5706)were prepared using solid dispersion-thin film hydration method.The encapsulation of the drug was characterized by Fourier transform infrared spectroscopy(FT-IR)and nuclear magnetic resonance hydrogen spectroscopy(1H-NMR).Drug loading capacity and encapsulation rate of the micelles were determined by ultraviolet spectroscopy(UV).The stability of the drug loaded micelles in vitro was examined,and the in vitro release pattern and in vivo tumor suppression effect were studied.The results showed that the micelles had homogeneous particle size,good stability and reduction-sensitive controlled drug release characteristics,and the inhibitory effect of the micelles on A549 lung adenocarcinoma was significantly stronger than that of the commercial available formulation nab- paclitaxel.

关 键 词：第三代紫杉烷 多药耐药 胶束 还原敏感 靶向控释 

分 类 号：O648[理学—物理化学]