摘要
目的:为了提高5-氟尿嘧啶(5-FU)抗结肠癌的口服疗效,构建了一种由N,N,N-三甲基-N-硬脂酰壳聚糖(TSCS)、腺苷和细胞穿透肽(TAT)共修饰的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,并对其进行相关评价。方法:合成TSCS、硬脂酰腺苷与5-FU磷脂复合物,制备了腺苷穿透肽共修饰纳米粒(AD-CPP-NPs),并对其进行粒径、包封率、体外释放等药剂学和细胞学评价。结果:纳米粒外观为类球形,分布均一。测得纳米粒粒径约为177 nm,Zeta电位为38.2 mV,包封率为56.6%。细胞实验表明,与HT-29细胞共孵育4 h后,与表面未修饰的PLGA纳米粒相比,共修饰纳米粒摄取能力相对聚乙烯醇纳米粒提高16.42倍。结论:共修饰纳米粒能主动靶向结肠癌细胞、增强细胞摄取效率、增加5-FU在癌细胞内的蓄积。
Objective:To improve the oral efficacy of 5-fluorouracil(5-FU)against colon cancer,PLGA nanoparticles co-modified by N,N,N-trimethyl-N-stearoyl chitosan(TSCS),adenosine and cell-penetrating peptide(TAT)were constructed and evaluated.Methods:TSCS,stearoyl adenosine and 5-fluorouracil phospholipid complexes were synthesized and co-modified nanoparticles AD-CPP-NPs were prepared and evaluated pharmacologically and cytologically in terms of particle size,encapsulation rate and in vitro release.Results:The nanoparticles were sphere-like in appearance and homogeneously distributed.The measured nanoparticle size was about 177 nm,the Zeta potential was 38.2 mV,and the encapsulation rate was 56.6%.Cellular experiments showed that after coincubation with HT-29 cells for 4 h,the uptake capacity of co-modified nanoparticles was increased by 16.42-fold relative to PVA-NPs compared to PLGA nanoparticles with unmodified surface.Conclusion:Co-modified nanoparticles can actively target colon cancer cells,enhance cell uptake efficiency,and increase the accumulation of 5-FU in cancer cells.
作者
赵月琪
罗梓涵
钟海军
熊远珍
方传洲
邓国兴
陈梁
童菲
郭锋
ZHAO Yue-qi;LUO Zi-han;ZHONG Hai-jun;XIONG Yuan-zhen;FANG Chuan-zhou;DENG Guo-xing;CHEN Liang;TONG Fei;GUO Feng(School of Pharmacy,Jiangxi Medical College,Nanchang University,Nanchang 330006,China;Jiangxi Puzheng Pharmaceutical Co.,Ltd.,Jian 343100,China;School of Stomatology,Nanchang University,Nanchang 330006,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2024年第6期580-587,共8页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(82060198,81560576)
江西省自然科学基金资助项目(20202BAB206083)。
关键词
壳聚糖
纳米粒
细胞穿膜肽
结肠癌
口服给药
chitosan
nanoparticles
cell-penetrating peptides
colon cancer
oral drug delivery