摘要
目的:制备麦胚凝集素(WGA)修饰的长春瑞滨(VRB)阳离子脂质体(WGA-VRB阳离子脂质体),优化处方并进行细胞毒性试验。方法:以磷脂、胆固醇为辅料,以3β-[N-(N′-N′-二甲基氨基乙烷)-氨基甲酰基]胆固醇盐酸盐(DC-Chol)为阳离子材料,以二硬脂酰磷脂酰乙醇胺-聚乙二醇2000(DSPE-PEG2000)为长循环链,采用薄膜分散法及硫酸铵梯度法制备WGA-VRB阳离子脂质体。以包封率为指标,采用星点设计-响应面法优化处方中DC-Chol、胆固醇和VRB用量。测定所制VRB脂质体和WGA-VRB阳离子脂质体中VRB含量,比较二者和空白阳离子脂质体作用于人乳腺癌细胞MCF-7和人非小细胞肺癌细胞A549后对细胞存活率的影响。结果:5 m L WGA-VRB阳离子脂质体的最优处方为磷脂22 mg、胆固醇12 mg、DC-Chol 8 mg、VRB 0.5 mg,其包封率为(92.24±1.21)%(n=3),与预测值的相对误差为5.3%。VRB脂质体和WGA-VRB阳离子脂质体中VRB含量分别为(96.01±3.26)、(93.39±1.59)μg/m L(n=3);与空白阳离子脂质体和VRB脂质体比较,WGA-VRB阳离子脂质体可明显降低MCF-7、A549细胞的存活率(P<0.05)。结论:成功制得WGA-VRB阳离子脂质体,其对MCF-7、A549细胞存活的抑制作用强于VRB脂质体。
OBJECTIVE:To prepare Wheat germ agglutinin(WGA)modified vinorelbine(VRB)cationic liposomes(WGA-VRB cationic liposomes),and to optimize the formulation and conduct cytotoxicity test.METHODS:Thin-film diffusion and ammonium sulfate gradient method were used to prepare WGA-VRB cationic liposomes using phospholipid and cholesterol as excipient,3β-[N-(N′-N′-dimethyl aminoethane)-carbamoyl]cholesterol hydrochloride(DC-Chol)as cationic material,distearoyl phosphatidylethanolamine-polyethylene glycol 2000(DSPE-PEG2000)as long cycle chain.Using encapsulation rate as index,central composite design-response surface methodology was used to optimize the amount of DC-Chol,cholesterol and VRB.The contents of VRB in VRB liposomes and WGA-VRB cationic liposomes were determined.The effects of them and blank cationic liposomes on survival rates of human breast cancer cell MCF-7 and human non-small cell lung cancer cells A549 were compared.RESULTS:The optimal formulation of 5 mL WGA-VRB cationic liposomes was as follows as phospholipid 22 mg,cholesterol 12 mg,DC-Chol 8 mg,VRB 0.5 mg.Encapsulation rate of the liposomes was(92.24±1.21)%(n=3),relative error of which to predicted value was 5.3%.The contents of VRB in VRB liposomes and WGA-VRB cationic liposomes were(96.01±3.26),(93.39±1.59)μg/mL(n=3).Compared with blank cationic liposomes and VRB liposomes,WGA-VRB cationic liposomes could significantly reduce survival rate of MCF-7 and A549.CONCLUSIONS:WGA-VRB cationic liposomes are prepared successfully.Inhibitory effect of WGA-VRB cationic liposomes on MCF-7 and A549 cell survival is stronger than that of VRB liposomes.
作者
肖瑶
王鑫
符敏
刘晶晶
李学涛
程岚
XIAO Yao;WANG Xin;FU Min;LIU Jingjing;LI Xuetao;CHENG Lan(School of Pharmacy,Liaoning University of TCM,Liaoning Dalian 116600,China)
出处
《中国药房》
CAS
北大核心
2018年第5期611-614,共4页
China Pharmacy
基金
国家自然科学基金资助项目(No.81541081
81673603)
关键词
麦胚凝集素
长春瑞滨
阳离子脂质体
处方优选
星点设计-响应面法
含量测定
Wheat germ agglutinin
Vinorelbine
Cationic liposomes
Formulation optimization
Central composite designresponse surface methodology
Content determination