摘要
目的以抗肿瘤药物紫杉醇(PTX)为模型药物,制备载紫杉醇聚(2-乙基-2-噁唑啉)(PEOz)修饰单壁碳纳米管递药系统(PTX@PEOz-SWCNT),对其进行理化性质、体外释药、生物相容性及体外抗肿瘤作用的评价。方法采用化学偶联合成PEOz-SWCNT,用紫外-可见吸收光谱法(UV-Vis)和红外光谱法(FTIR)对合成产物进行表征,并对其粒径和电位进行测定;制备载药复合物PTX@PEOz-SWCNT,测定其载药量和包封率,透析法进行体外释药试验;体外溶血试验评价载体材料的安全性,MTT法评价载体材料生物相容性及载药复合物对MCF-7细胞的生长抑制率,用荧光倒置显微镜考察了香豆素-6(C6)标记载体在MCF-7细胞中的摄取。结果 PEOz-SWCNT材料的平均粒径为(219.8±2.9)nm,Zeta电位值为(-35.23±0.74)mV,PTX@PEOz-SWCNT的载药量为(38.19±0.74)%,包封率为(94.38±0.94)%;载药复合物在pH 5.0的条件下释药明显加快,表现出明显的pH响应性;体外溶血试验结果表明,PEOz-SWCNT质量浓度在0.4mg/mL以下无明显溶血反应,PEOz-SWCNT材料在细胞水平生物相容性良好,PTX@PEOz-SWCNT对MCF-7细胞的生长抑制率显著增强;与C6@SWCNT相比,C6@PEOz-SWCNT载药复合物的细胞摄取增加。结论 PTX@PEOz-SWCNT递药系统在肿瘤靶向给药方面具有一定的应用前景。
Objective To prepare a PEOz modified single-walled carbon nanotube delivery system(PEOz-SWCNT) with the antitumor drug paclitaxel(PTX) as a model drug(PTX@PEOz-SWCNT) and evaluate its physical and chemical properties, in vitro drug release, biocompatibility, and in vitro antitumor effects. Methods PEOz-SWCNT was synthesized by chemical coupling method, and the products were characterized by UV-Vis spectroscopy(UV-Vis) and infrared spectroscopy(FTIR). The particle size and Zeta potential of PEOz-SWCNT were measured. The drug-loaded complex PTX@PEOz-SWCNT was prepared and the loading efficiency and encapsulation efficiency were measured. The dialysis method was used for in vitro drug release. The safety of the application of PEOz-SWCNT was evaluated by in vitro hemolysis test. The MTT method was used to evaluate the biocompatibility of the material and the growth inhibition rate of the drug-loaded complex on MCF-7 cells. The uptake of Coumarin-6(C6)-labeled vector in MCF-7 cells was examined by fluorescence inversion microscope. Results The average particle size of PEOz-SWCNT was(219.8 ± 2.9) nm and the Zeta potential was(-35.23 ± 0.74) mV. The loading efficiency of PTX@PEOz-SWCNT was(38.19 ± 0.74) %, and the encapsulation efficiency was(94.38 ± 0.94)%. The drug release rate was significantly accelerated at p H 5.0, showing obvious pH responsiveness. There was no obvious hemolysis when the concentration of PEOz-SWCNT was below 0.4 mg/mL. The biocompatibility of PEOz-SWCNT on Hela cells was good, and the PTX@PEOz-SWCNT could significantly enhance the cell growth inhibition rate on MCF-7 cells. The in vitro antitumor activity test results showed that the cell uptake of the C6@PEOz-SWCNT was increased compared to C6@SWCNT. Conclusion PTX@PEOz-SWCNT drug delivery system is promising in tumor-targeted drug delivery.
作者
王小宁
闫梦茹
马远涛
梁晓燕
罗国平
WANG Xiao-ning;YAN Meng-ru;MA Yuan-tao;LIANG Xiao-yan;LUO Guo-ping(College of Pharmacy,Xi’an Medical University,Xi’an 710021,China)
出处
《中草药》
CAS
CSCD
北大核心
2020年第3期607-615,共9页
Chinese Traditional and Herbal Drugs
基金
陕西省科技厅面上项目(2018JM7092)
陕西省科技厅面上项目(2018JM7089)
陕西省教育厅专项科研计划项目(19JK0757)
西安医学院中尼友好拉吉姆医学实验室开放基金项目(18LJM06)
2018年省级大学生创新创业训练项目计划项目(201825055)
西安医学院2017年国家基金培育项目(2017GJFY10)
陕西高校青年创新团队建设项目(陕教[2019] 90号).
