普鲁兰多糖修饰的人参皂苷Rg3纳米结构脂质载体促吸收及其体外抗肿瘤评价  

Effect of ginsenoside Rg nanostructured lipid carrier modified by pullulan on promoting absorption and its anti-tumor evaluation in vitro

作　　者：杨青 蔡宁[1] 车道标[1] 金鑫[1] YANG Qing;CAI Ning;CHE Dao-biao;JIN Xin(Department of Pharmacy,Suqian First Hospital,Suqian Branch Jiangsu Province Hospital,Suqian 223800,China)

机构地区：[1]江苏省人民医院宿迁分院宿迁市第一人民医院药学部,江苏宿迁223800

出　　处：《中国中药杂志》2020年第21期5184-5192,共9页China Journal of Chinese Materia Medica

基　　金：江苏省自然科学基金面上项目(BK20171321);宿迁市科技计划项目(S201725)。

摘　　要：人参皂苷Rg3作为抗肿瘤辅助用药,广泛应用于临床,但由于其口服吸收差,因此应用受到了一定的限制。该研究拟构建普鲁兰多糖(pullulan,PUL)修饰的人参皂苷Rg3纳米结构脂质载体(PUL-Rg3-NLC),提高Rg3的黏附特性,促进摄取,改善抗肿瘤功效。通过形态学观察、粒径大小、Zeta电位等指标对PUL-Rg3-NLC进行表征。通过口服灌胃实验评价其体内黏附特性,并结合体外摄取行为、体外抗肿瘤药效学等评价手段多角度进行验证。结果表明,实验制备的PUL-Rg3-NLC粒径为(102±1.89)nm,具有胃黏附特性,可以较长时间地滞留在胃组织,其主要通过细胞膜穴样凹陷介导的内吞途径促进人胃腺癌细胞BGC-823细胞对其摄取。体外MTT、凋亡、划痕和侵袭实验均表现出一定的抗肿瘤作用。因此,PUL-Rg3-NLC可以显著促进人参皂苷Rg3在胃部的黏附,促进胃癌细胞对药物的摄取,提高抗肿瘤作用,该研究可为胃部肿瘤辅助治疗提供一定的借鉴。Ginsenoside Rg3 is widely used in clinical practice as an anti-tumor adjuvant drug,but its application is limited due to its poor oral absorption.In this study,we intended to construct a ginsenoside Rg3 nanostructured lipid carrier modified by the pullulan(PUL-Rg3-NLC)to improve the adhesion properties of ginsenoside Rg3,promote the drug uptake and improve the anti-tumor efficacy.PUL-Rg3-NLC was characterized by morphology,particle size and Zeta potential.In vivo adhesion characteristics were evaluated by oral gavage tests,and the results were verified from multiple perspectives in combination with in vitro uptake behavior and in vitro pharmacodynamics.The results showed that PUL-Rg3-NLC,with a particle size of(102±1.89)nm,was characterized by gastric adhesion and could be retained in gastric tissues for a long time,and its uptake by BGC-823 cells was promoted mainly through the pathway mediated by the caveolin-mediated endocytosis.In vitro MTT,cell apoptosis,wound-healing assay and invasion assay all showed some anti-tumor effects.Therefore,PUL-Rg3-NLC can significantly promote the adhesion of Rg3 in the stomach,promote the uptake of drugs by gastric cancer cells,and improve the anti-tumor effect.This study can provide some reference for the adjuvant treatment of gastric cancer.

关 键 词：纳米结构脂质载体 黏附 普鲁兰多糖 摄取 人参皂苷RG3 

分 类 号：R285[医药卫生—中药学]