磷脂组成对马钱子总生物碱隐形脂质体静脉注射后马钱子碱组织分布的影响

目的:考察磷脂组成对马钱子总生物碱隐形脂质体静脉注射后马钱子碱在体内分布的影响。方法:采用硫酸铵梯度法和隐形脂质体技术制备马钱子总生物碱脂质体,除去游离药物后,利用HPLC测定马钱子碱的含量,流动相乙腈-0.01mol·L-1庚烷磺酸钠与0.02 mol·L-1磷酸二氢钾等量混合液(24∶76),检测波长264 nm。比较马钱子总生物碱溶液和不同磷脂组成马钱子总生物碱隐形脂质体静脉注射给药后马钱子碱的组织分布情况。结果:不同磷脂组成脂质体中马钱子碱占总生物碱的质量分数在26%~31%。与大豆磷脂隐形脂质体相比,马钱子总生物碱复合磷脂隐形脂质体静脉注射给药5 min后在血液和小肠中的浓度分别增加了2.35,1.34倍;而氢化大豆磷脂隐形脂质体在血液中的浓度极显著增加,给药后5 min的浓度增加了8.52倍,并且在脾、肺、心等组织中的浓度也明显增加,在小肠中浓度显著下降。结论:磷脂组成对马钱子总生物碱隐形脂质体的体内分布有显著影响。

Effect of Phospholipids Composition on Tissue Distribution of Brucine in Rats After Intravenous Administration of Stealth Liposomes Containing Total Alkaloids from Strychni Semen

Objective: To investigate effect the of phospholipids composition on tissue distribution characteristics of brucine in stealth liposomes containing total alkaloids from Strychni Semen. Method: Liposomes containing total alkaloids from Strychni Semen were prepared by ammonium sulfate transmembrane gradients and stealth liposome technique.Contents of total alkaloids and brucine in liposomes were determined and compared after free drug was removed.After intravenous administration of total alkaloids solution or stealth liposomes with different composition,tissue and plasma samples were drawn at different intervals and the concentration of brucine were determined by a validated HPLC method. Result: Ratio of brucine to total alkaloids in liposomes,in the range of 26%-31%,hardly varied with phospholipids composition.Compared with soybean phosphatidylcholine (SPC) stealth liposomes,after intravenous administration of stealth liposomes composed of both hydrogenated soybean phosphatidylcholine (HSPC) and SPC,the concentration of burcine in small intestine and plasma at 5 min were significantly increased 1.34-fold and 2.35-fold,respectively.Moreover,following administration of HSPC stealth liposomes containing total alkaloids,plasma concentration of brucine was much higher than other liposomes.Compared with SPC liposomes,plasma concentration of brucine at 5 min increased by 8.52-fold.In addition,brucine concentration in spleen,lung and heart were also significantly increased and those in small intestine were significantly reduced. Conclusion: Phospholipids composition is the key factor which influences tissue distribution of brucine after intravenous administration of stealth liposomes containing total alkaloids from Strychni Semen.