多肽K237修饰的紫杉醇长循环靶向脂质体的制备及体外评价  

Preparation and in vitro evaluation of paclitaxel-loaded K237-long-circulating targeted liposome

作　　者：胡戴[1,2] 谢向阳[1] 陆媛媛[1,2] 刘宏[1] 符旭东[1] 

机构地区：[1]广州军区武汉总医院药剂科,湖北武汉430070 [2]湖北中医药大学药学院,湖北武汉430065

出　　处：《中国医院药学杂志》2013年第11期856-861,共6页Chinese Journal of Hospital Pharmacy

基　　金：湖北省科技计划自然科学基金项目(编号:2011CDB019)

摘　　要：目的:制备由多肽K237介导的紫杉醇长循环靶向脂质体(K237-PTX-Lip),考察其体外对人卵巢癌上皮细胞(SK-OV-3)和人脐静脉内皮细胞(HUVEC)两种细胞的抑制作用。方法:采用NH2末端PEG化技术合成DSPE-PEG-K237,以此作为K237-PTX-Lip的向导材料,采用薄膜分散法制备K237-PTX-Lip,高效液相色谱法测定紫杉醇的含量,透射电镜观察K237-PTX-Lip的形貌,激光粒度仪测量其粒径,MTT法和荧光显微观察其对SKOV-3和HUVEC体外增殖的抑制作用。结果:K237-PTX-Lip和紫杉醇普通脂质体(PTX-Lip)的包封率为(93.0±0.9)%和(98.0±1.3)%,粒径为(78.2±6.1)nm和(54.6±4.7)nm。体外细胞实验结果显示,K237-PTX-Lip对SKOV-3和HUVEC的细胞毒(IC50)分别为(25.1±4.8)nmol·L-1和(8.8±0.6)nmol·L-1是PTX-Lip的0.336倍和0.695倍。结论:K237的修饰在不影响脂质体理化性质的同时增加了其对细胞的靶向性,从而增加了细胞毒性,为肿瘤的靶向治疗提供了新的思路。OBJECTIVE To encapsulate paclitaxel within K237 modified long-circulating targeted liposome（K237-PTX-Lip） and to study its in vitro inhibitory effect on SKOV3 and HUVEC. METHODS DSPE-PEG-K237 was synthesized by conjuga ting the amino group of K237 to the terminal NHS form DSPE PEG-NHS,which was used as liposome materials to obtain the paclitaxel loaded liposome. K237 PTX Lip was prepared by film dispersion method,content of paclitaxel in K237 PTX Lip was determined by HPLC. TEM was used to observe the morphology of K237-PTX-Lip. Particle size and potential was measured by laser particle size analyzer, MTT experiment and fluorescence microscopy was adopted to evaluate the inhibitory effect of K237 PTX-Lip on SKOV-3 and HUVEC cells. RESULTN The encapsulation efficiencies of K237-PT-Lip and paclitaxel liposome （PTX Lip） were （93.0 ± 0. 9）% and （98. 0± 1.3）%, particle sizes were （78. 2 ± 6. 1 ）nm and （54. 6± 4. 7）nm. The cytotoxici- ties（IC50 ） of K237-PTX-Lip on SKOV-3 and HUVEC cells were （25. 1 ± 4. 8）nmol.L^-1 and （8.8 ± 0. 6）nmol. L^-1 , which was increased by 0. 336 fold in SKOV-3 and 0. 695 fold in HUVEC, compared with PTX-Lip. CONCLUSION K237 modification could increase the targeting efficiency of liposome on tumor cell, thus resulting in higher cytotoxicities in comparison with PTX- Lip,which might be a potential formulation for targeting cancer therapy.

关 键 词：脂质体 紫杉醇 K237 

分 类 号：R943[医药卫生—药剂学]