基于叶酸表面修饰的蓝萼甲素长循环脂质体的制备与药效学评价  

Preparation and pharmacodynamic evaluation of folic acid-surface modified glaucocalyxin A PEGylated liposomes

作　　者：郝宁 于佳[1] HAO Ning;YU Jia(Department of Pharmacy,the Second Hospital Affiliated to Dalian Medical University,Dalian 116207,China)

机构地区：[1]大连医科大学附属第二医院药学部,辽宁大连116207

出　　处：《沈阳药科大学学报》2021年第6期553-558,583,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的制备叶酸-聚乙二醇2000-二棕榈酰磷脂酰乙醇胺(FA-PEG2000-DSPE)表面修饰的蓝萼甲素长循环脂质体,并评价其对人宫颈癌Hela细胞的体内外抗肿瘤活性。方法采用薄膜分散-挤出法分别制备蓝萼甲素长循环脂质体(GLA-Lips)和经FA-PEG2000-DSPE修饰的蓝萼甲素长循环脂(FA-GLA-Lips),通过透射电镜观察GLA-Lips和FA-GLA-Lips的微观形态,马尔文激光粒度仪测定了两种脂质体的粒径分布以及ζ电位,采用反向透析法考察了GLA-Lips和FA-GLA-Lips在磷酸盐缓冲液(pH7.4)和大鼠血浆中的药物释放情况;比较了蓝萼甲素原料药、GLA-Lips和FA-GLA-Lips在体外和体内对人宫颈癌Hela细胞的抗肿瘤效果。结果透射电镜下可观察到GLA-Lips和FA-GLA-Lips均呈类球状分布,平均粒径分别为(93.5±2.1)nm和(89.4±3.7)nm,ζ电位分别为(-12.4±0.6)mV和(-11.2±0.7)mV;GLA-Lips和FA-GLA-Lips在磷酸盐缓冲液中药物释放缓慢,而在大鼠血浆药物释放速率提高;体外实验结果显示GLA-Lips和FA-GLALips对人宫颈癌Hela细胞的抑制作用均高于蓝萼甲素原料药,裸鼠体内实验结果显示FA-GLALips抑制人宫颈癌Hela细胞生长速度高于GLA-Lips。结论本研究制备的叶酸表面修饰蓝萼甲素长循环脂质体对人宫颈癌Hela细胞具有较强的抑制效果,具有一定的靶向性。Objective To prepare folic acid-polyethylene glycol 2000-dipalmitoylphosphatidy-lethanolamine(FA-PEG2000-DSPE)surface modified glaucocalyxin A PEGylated liposomes and evaluate its anti-tumor effect on human cervical cancer HeLa cells in vitro and in vivo.Methods The glaucocalyxin A PEGylated liposomes(GLA-Lips)and folic acid-surface modified glaucocalyxin A PEGylated liposomes(FA-GLALips)were prepared by thin film dispersion-extrusion method.The microscopic morphology of GLA-Lips and FA-GLA-Lips was observed under transmission electron microscopy.The particle size distribution andζpotential of the GLA-Lips and FA-GLA-Lips were measured by a Malvern laser particle size analyzer.The drug release of GLA-Lips and FA-GLA-Lips in phosphate buffered saline(pH 7.4)and rat plasma was examined by reverse dialysis.The antitumor activity of glaucocalyxin A,GLA-Lips and FA-GLA-Lips on human cervical cancer Hela cells in vitro and in vivo were compared.Results Under transmission electron microscopy,the GLA-Lips and FA-GLA-Lips were observed to be spheroidal,with average particle diameters of(93.5±2.1)nm and(89.4±3.7)nm,andζpotentials were(-12.4±0.6)mV and(-11.2±0.7)mV;The GLA-Lips and FA-GLA-Lips drug release was slower in phosphate buffer(pH 7.4),while drug release was faster in rat plasma.The experiments showed that GLA-Lips and FA-GLA-Lips have a higher inhibitory effect on human cervical cancer Hela cells than that of glaucocalyxin A in vitro.And FA-GLA-Lips inhibited the growth of human cervical cancer Hela cells in nude mice significantly higher than GLA-Lips in vivo.Conclusion The FA-GLA-Lips have good inhibitory activity for human cervical cancer Hela cells,which have certain targeting.

关 键 词：蓝萼甲素 叶酸-聚乙二醇2000-二棕榈酰磷脂酰乙醇胺 长循环脂质体 薄膜分散-挤出法 人宫颈癌HELA细胞 抗肿瘤活性 

分 类 号：R94[医药卫生—药剂学]