叶酸受体靶向β-榄香烯固体脂质纳米粒的制备及其大鼠体内分布  

Preparation and Tissue Distribution of Folate Receptor-Targeted Solid Lipid Nanoparticle for β-Elemene in Rats

作　　者：王艳芝[1] 周婕[1] 郑甲信[1] 徐炳欣[1] 毕殿洲[2] 邓意辉[2] 

机构地区：[1]郑州大学药学院,郑州450001 [2]沈阳药科大学药学院,沈阳110016

出　　处：《中国药学杂志》2009年第12期920-925,共6页Chinese Pharmaceutical Journal

摘　　要：目的研究叶酸复合物修饰β-榄香烯固体脂质纳米粒(SLN)制剂在大鼠体内的药动学与组织分布情况。方法脂质中加入聚乙二醇单甲醚胆固醇琥珀酸酯(CHS-PEG)和N-硬脂酰基-N′-蝶酰谷氨酰基-聚乙二醇二胺(FA-PEG-S),采用超声-挤压过滤法制备叶酸受体靶向β-榄香烯SLN制剂(FA-PEG-SLN)并加以表征。大鼠尾静脉给药,HPLC测定该制剂的药动学特征及组织分布情况,与普通β-榄香烯SLN(SLN-1)及榄香烯注射乳剂的相比较。结果静脉给药后,FA-PEG-SLN在血浆中的消除半衰期为44.0min,显著长于SLN-1和乳剂的15.6和15.4min。与SLN-1相比,FA-PEG-SLN5min时在肝肾中的药物浓度较高,在脾中稍低。30和60min时,FA-PEG-SLN组在除肺外的各组织中的β-榄香烯浓度皆显著高于SLN-1组和乳剂组。结论FA-PEG-SLN能够在血浆中较长时间循环,在主要器官中的浓度较高且消除速度较慢,有进一步研究的价值。OBJECTIVE To study the tissue distribution of β-elemene SLN designed for targeting of folate receptor in rats after an intravenous administration. METHODS Monomethoxy polyethylene glycol（2000）succinyl cholesterol（CHS-PEG） and N-stearyl-N＇-pteroylglutamyl-polyethylene glycol（3350） bis-amine （FA-PEG-S） were added into the formulation of common β-elemene SLN（SLN-1） to prepare folate receptor-targeted solid lipid nanoparticle for β-elemene （FA-PEG-SLN） by supersonic and membrane-extrusion method. The pharmacokinetic profiles and tissue distribution of β-elemene were investigated after i.v. administration of different formulations（SLN-1, FA-PEG-SLN and emulsion）, β-elemene levels in plasma and tissues were determined by HPLC. RESULTS The t1/2 of FA-PEG-SLN containing 4% CHS-PEG and 0.1% FA-PEG-S （molecular ratio） was 44.0 min which was longer than those of SLN-1 and emulsion. Furthermore, tissue distribution of FA-PEG-SLN was different from those of SLN-1 and emulsion, β-elemene levels of FA-PEG-SLN were higher in the liver and kidney and lower in the spleen compared with that of SLN-1 5 min after injection. After 30 and 60 min, β-elemene concentration in tissues except lung was higher for FA-PEG-SLN than those of SLN-1 and emulsion. CONCLUSION FA-PEG-SLN could circulate in blood for a longer time and reach higher concentration in many tissues with slow elimination. FA-PEG-SLN is an attractive candidate for further research.

关 键 词：Β-榄香烯 固体脂质纳米粒 叶酸受体 体内分布 大鼠 

分 类 号：R944[医药卫生—药剂学]