新型棕榈酰谷氨酸-顺铂纳米粒的制备及其体外药效研究  

The investigation of the preparation and in vitro pharmacodynamics of new palmoyl glutamic acidcisplatin nanoparticles

作　　者：任伟芳 宋娟[1] 朱珊珊[1] 徐婷婷[1] 杨丽[1] 丁平田[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2016年第12期927-931,共5页Journal of Shenyang Pharmaceutical University

摘　　要：目的以棕榈酰谷氨酸为载体材料制备新型高载药顺铂纳米粒(palmoyl glutamic acid-cisplatin-nanoparticles,PG-CDDP-NPs),并对其体外抗肿瘤活性进行研究。方法采用肖顿-鲍曼缩合法合成棕榈酰谷氨酸两亲性材料,以所合成的材料为载体,利用其与顺铂的配位作用制备高载药新型顺铂纳米粒,并对所制备的PG-CDDP-NPs性质进行考察;以市售顺铂注射剂为对照,采用MTT法考察了PG-CDDP-NPs对人肝癌细胞HEPG2的体外抗肿瘤活性。结果合成了棕榈酰谷氨酸,并成功制备了高载药量的PG-CDDP-NPs,PG-CDDP-NPs粒径为(106.33±4.45)nm,粒度分布较均匀,包封率为(84.20±0.81)%,载药量质量分数高达(27.03±0.12)%。体外释放研究表明,PG-CDDP-NPs具有缓慢释药性质,24 h累积释放量质量分数仅为(28.74±1.37)%。体外药效学实验结果显示PG-CDDP-NPs和CDDP-S对高表达的人肝癌细胞HEPG2细胞的IC50值分别为3.54μmol·L-1和4.55μmol·L-1。结论以棕榈酰谷氨酸为载体材料可制备高载药量的顺铂纳米粒;PG-CDDP-NPs在体外对HEPG2细胞有杀伤作用,与顺铂注射剂相比,显示出较强的抑瘤效果,PG-CDDP-NPs是一种具有潜在应用价值的顺铂纳米制剂。Objective To prepare novel cisplatin nanoparticles（ PG-CDDP-NPs） with high drug-loading utilizing palmoyl glutamic acid as carrier materials and investigate its anticancer activity in vitro. Methods Palmoyl glutamic acid as amphiphilic materials was synthesized by Schotten-Baumann condensation synthesis method. PG-CDDP-NPs were prepared by using the synthetic materials to coordinate with CDDP and the properities of PG-CDDP-NPs were inspected. MTT method was applied to determine the in vitro anticancer activity of PG-CDDP-NPs in HEPG2 compared with CDDP-S. Results Palmoyl glutamic acid was successfully synthesized and PG-CDDP-NPs with high drug-loading was formulated. The particle size of PG-CDDP-NPs was（ 106. 33 ± 4. 45） nm with uniform particle size distribution,of which the entrapment efficiency was（ 84. 20 ± 0. 81） % and the drug loading rate reached at（ 27. 03 ± 0. 12） %. The results of the in vitro release of PG-CDDP-NPs exhibited that the cumulative release amount of 24 h was（ 28. 74 ±1. 37） % indicating that PG-CDDP-NPs had the good quality of slowreleasing. The pharmacodynamics in vitro experiment results revealed that the values of PG-CDDP-NPs and CDDP-S in HEPG2 were3. 54 μmol·L^- 1and 4. 55 μmol·L^- 1,respectively. Conclusions Palmoyl glutamic acid,the carrier material,can prepare the high drug-loading CDDP nanoparticles. PG-CDDP-NPs are more effective in killing HEPG2 in vitro and showstronger antitumor effect comparing with CDDP-S,which may be hopeful to be a kind of potential preparation of CDDP nanoparticles.

关 键 词：顺铂 棕榈酰谷氨酸 缓释 纳米粒 体外药效 

分 类 号：R94[医药卫生—药剂学]