冰片修饰的姜黄素阳离子脂质体的制备及其脑靶向作用研究

Preparation of Curcumin-loaded Modifying Borneol Cationic Liposomes and Study on Its Brain Targeting Effect

关键词:  冰片|姜黄素|阳离子脂质体|药动学

Key words:  borneol|curcumin|cationic liposomes|pharmacokinetics

摘要:

目的 制备冰片修饰的姜黄素阳离子脂质体（curcumin-loaded modifying borneol cationic liposomes，Cur-BCLPs），鼻腔给药后考察其在大鼠体内的药动学行为并对其脑组织分布进行研究。方法 采用乙醇注入法制备Cur-BCLPs；透射电镜观察阳离子脂质体的形态；激光粒度仪考察粒径；超速离心法测定其包封率及载药量；以姜黄素混悬液（curcumin suspension，Cur-Sol）和冰片-姜黄素混悬液（borneol curcumin suspension，BO-Cur-Sol）为对照组，考察大鼠鼻腔给药Cur-BCLPs的体内药动学过程，并测定其在大鼠脑组织的浓度，运用DAS 2.0软件拟合药动学参数。结果 阳离子脂质体外观呈圆形或类圆形，平均粒径为（105.99±2.40）nm，包封率和载药量分别为（81.95±1.03）%和（4.28±0.46）%；体内药动学结果显示，Cur-Sol、BO-Cur-Sol和Cur-BCLPs的半衰期（T_1/2）分别为（4.27±1.53）h，（3.98±0.24）h和（6.01±0.63）h，AUC_0→t分别为（224.38±21.95）μg·h·L^-1，（243.40±12.26）μg·h·L^-1和（562.28±24.30）μg·h·L^-1，清除率分别为（1.82±0.36）L·h^-1·kg^-1，（1.72±0.11）L·h^-1·kg^-1和（0.78±0.03）L·h^-1·kg^-1，滞留时间分别为（4.28±0.23）h，（4.41±0.15）h和（8.09±0.17）h。脑组织分布结果显示，Cur-Sol、BO-Cur-Sol和Cur-BCLPs的AUC_0→t分别为（29.82±1.10）μg·h·g^-1，（35.47±1.75）μg·h·g^-1和（54.06±3.90）μg·h·g^-1，清除率分别为（15.73±0.84）L·h^-1·kg^-1，（13.23±0.52）L·h^-1·kg^-1和（8.52±0.92）L·h^-1·kg^-1。结论 Cur-BCLPs经鼻腔给药后显著提高姜黄素体内和脑组织蓄积量并且延缓消除。

Abstract:

OBJECTIVE To prepare curcumin-loaded modifying borneol cationic liposomes(Cur-BCLPs), and to investigate their pharmacokinetics in vivo and the brain tissue distribution after intranasal administration. METHODS Cur-BCLPs were prepared with ethanol injection method; the morphology of cationic liposomes was observed by transmission electron microscope; mean particle size was estimated by laser particle size analyzer; entrapment efficiency and drug loading were investigated by ultracentrifugation; using curcumin suspension(Cur-Sol) and borneol curcumin suspension(BO-Cur-Sol) as control group, the pharmacokinetic behavior in vivo and the concentration in brain of Cur-BCLPs after intranasal administration in rats were studied. The pharmacokinetic parameters were calculated by DAS 2.0. RESULTS The shape of cationic liposomes was roundness. The mean particle size was (105.99±2.40)nm, entrapment efficiency was (81.95±1.03)%, drug loading was (4.28±0.46)%, respectively. Results of pharmacokinetic study in vivo showed that the T_1/2 of Cur-Sol, BO-Cur-Sol and Cur-BCLPs were (4.27±1.53)h, (3.98±0.24)h and (6.01±0.63)h, AUC_0→t were (224.38±21.95)μg·h·L^-1, (243.40±12.26)μg·h·L^-1 and (562.28±24.30)μg·h·L^-1, clearance rate were (1.82±0.36)L·h^-1·kg^-1, (1.72±0.11)L·h^-1·kg^-1 and (0.78±0.03)L·h^-1·kg^-1,mean residence time were (4.28±0.23)h, (4.41±0.15)h and (8.09±0.17)h. Results of distribution in brain showed that AUC_0→tof Cur-Sol, BO-Cur-Sol and Cur-BCLPs were (29.82±1.10)μg·h·g^-1, (35.47±1.75)μg·h·g^-1 and(54.06±3.90)μg·h·g^-1, clearance rate were (15.73±0.84)L·h^-1·kg^-1, (13.23±0.52)L·h^-1·kg^-1and (8.52±0.92)L·h^-1·kg^-1. CONCLUSION Cur-BCLPs after intranasal administration may increase the concentration and slow their elimination in vivo and brain.