阿可拉定长循环脂质体的制备与药效学评价  

Preparation and pharmacodynamic evaluation of icaritin PEGylated liposomes

作　　者：付淑凤[1] 马丽霞[2] FU Shufeng;MA Lixia(Xianyang Vocational College,Xianyang 712000,China;Health Science Center,Xi'an Jiaotong University,Xi'an 710000,China)

机构地区：[1]咸阳职业技术学院,咸阳712000 [2]西安交通大学医学部,西安710000

出　　处：《西北药学杂志》2023年第1期113-117,共5页Northwest Pharmaceutical Journal

摘　　要：目的制备阿可拉定长循环脂质体(icaritin PEGylated liposomes,Ica-Lips),并评价其对人源肝癌细胞(hepaloblasloma G2,HepG2)的体内抗肿瘤效果。方法采用冷冻干燥-水化法制备Ica-Lips,并在透射电镜下观察Ica-Lips的微观形态,测定Ica-Lips的包封率、粒径分布、Zeta电位,以及在pH7.4磷酸盐缓冲液(PBS)以及大鼠血浆中的药物释放特性;并考察了Ica-Lips的稳定性;比较了Ica-Lips与Ica原料药在大鼠体内的药动学行为,评价Ica-Lips对小鼠接种人源肝癌细胞(HepG2)的抑瘤效果。结果制备的Ica-Lips呈类球状分布,其包封率为96.4%±0.3%,平均粒径为(108.4±3.6)nm,Zeta电位为(-12.9±0.2)mV;与Ica-Lips在pH7.4 PBS中的释药速率相比,其在大鼠血浆中的释药速率明显加快;Ica-Lips在低温条件下保存3个月,稳定性良好;药动学研究表明,Ica-Lips可显著延长药物在大鼠体内的滞留时间,增加药物的生物利用度;药效学研究表明,Ica-Lips对小鼠接种人源肝癌细胞(HepG2)的抑瘤效果显著高于Ica溶液(P<0.05)。结论将阿可拉定制备成长循环脂质体,提高了抗肿瘤效果,具有潜在的临床应用价值。Objective To prepare icaritin PEGylated liposomes(Ica-Lips),and to evaluate its antitumor effect on human hepatoma cells(HepG2)in vivo.Methods The Ica-Lips were prepared by freeze drying-hydration method,and the Ica-Lips were observed under transmission electron microscope.The encapsulation efficiency,particle size distribution,Zeta potential of Ica-Lips were determined,and the drug release characteristics of Ica-Lips in pH 7.4 phosphate buffer and rat plasma were compared.The stability of Ica-Lips was investigated.The pharmacokinetics of Ica-Lips and Ica active pharmaceutical ingredients(API)in rats were compared,and the tumor-inhibitory effect of Ica-Lips on mice inoculated with HepG2 cells was evaluated.Results The Ica-Lips showed a quasi-spherical distribution,the encapsulation efficiency was 96.4%±0.3%,the average particle size was(108.4±3.6)nm,and the Zeta potential was(-12.9±0.2)mV.Compared with the drug release rate in pH7.4 phosphate buffer,the drug release rate of Ica-Lips in rat plasma was significantly accelerated.Ica-Lips could be stored at low temperature for 3 months with good stability.Pharmacokinetics in rats showed that Ica-Lips could significantly prolong the residence time in rats and increase the bioavailability.Pharmacodynamics showed that the tumor-inhibitory effect of Ica-Lips in mice inoculated with HepG2 cells was significantly higher than that of Ica solution(P<0.05).Conclusion In this study,Ica was prepared into PEGylated liposomes,which improved the anti-tumor effect,and have potential clinical application value.

关 键 词：阿可拉定 长循环脂质体 人源肝癌细胞(HepG2) 冷冻干燥-水化法 抗肿瘤效果 

分 类 号：R94[医药卫生—药剂学]