摘要
目的优选转铁蛋白(Tf)修饰蛇床子素(Ost)长循环脂质体(Tf-Ost-Lip)的处方,并考察其体外跨越血脑屏障的能力。方法利用薄膜分散法制备Tf-Ost-Lip,以Ost包封率为考察指标,采用星点设计-响应面法优化卵磷脂(EPC)浓度(mg/mL),EPC与胆固醇(Chol)质量比(mg/mg),EPC与Ost质量比(mg/mg),测定各脂质体中Ost的包封率。构建血脑屏障体外模型,比较蛇床子素长循环脂质体(Ost-Lip)跨越血脑屏障的能力。结果通过星点设计-效应面法,确定了该脂质体的最优处方为EPC浓度为5.12 mg/mL,EPC与Chol质量比为4.89(mg/mg),EPC与Ost质量比为17.67(mg/mg)。按照优选出的最佳处方,以EPC、Chol、DSPE-PEG_(2000)及Tf-DSPE-PEG_(2000)为膜材制备的Tf-Ost-Lip的包封率为91%以上。体外细胞摄取实验结果表明,hCMEC/D3细胞对Tf-Ost-Lip的摄取效率与Ost-Lip相比显著提高。结论成功优化适用于制备Ost-Lip的处方,Ost-Lip经过Tf修饰后,其跨血脑屏障的能力显著增强,被认为是一种潜在的高效的脑靶向纳米给药系统。
Objective To optimize the formulation of transferrin(Tf)modified Osthole(Ost)long circulating liposomes(Tf-Ost-Lip),and investigate its ability to cross the blood-brain barrier in vitro.Methods Tf-Ost-Lip was prepared by the thin film dispersion method,and the encapsulation rate of Ost was used as the indicator.The central composite design-response surface method was used to optimize the lecithin(EPC)concentration(mg/mL).The mass ratio of EPC to cholesterol(Chol)(mg/mg)and the mass ratio of EPC to Ost(mg/mg)were used to determine the encapsulation efficiency of Ost in liposomes.An in vitro model of the blood-brain barrier was constructed to compare the ability of osthole long-circulating liposomes(Ost-Lip)to cross the blood-brain barrier.Results The optimal formulation of the liposome was determined to be EPC concentration of 5.12 mg/mL,EPC to Chol mass ratio of 4.89 mg/mg,EPC to Ost mass ratio of 17.67 mg/mg.According to the optimal prescription,the encapsulation efficiency of Tf-Ost-Lip prepared with EPC,Chol,DSPE-PEG_(2000) and Tf-DSPE-PEG_(2000) as membrane materials was over 91%.The in vitro cell uptake results showed that the uptake efficiency of Tf-Ost-Lip by hCMEC/D3 cells was significantly higher than that of Ost-Lip.Conclusion The prescription suitable for the preparation of Ost-Lip was successfully optimized.After Ost-Lip was modified with Tf,its ability to cross the blood-brain barrier was significantly enhanced,and it was considered as a potential and efficient brain-targeted nano-drug system.
作者
程岚
孔亮
杨静娴
李学涛
CHENG Lan;KONG Liang;YANG Jingxian;LI Xuetao(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,Liaoning,China)
出处
《辽宁中医杂志》
CAS
2021年第11期150-154,225,共6页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81673603,81874347)
关键词
转铁蛋白
蛇床子素
脂质体
血脑屏障
脑靶向
transferrin
osthole
liposomes
blood-brain barrier
brain targeting