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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 pharmacokinetics and tissue distribution of β-elemene solid lipid nanoparticles (SLN) modified by folate in rats. Methods Lipid was added with polyethylene glycol monomethyl ether cholesterol succinate (CHS-PEG) and N-stearoyl-N’-bexyl glutamyl-polyethylene glycol diamine (FA- , The folate receptor targeting β-elemene SLN preparation (FA-PEG-SLN) was prepared and characterized by ultrasonic-squeeze filtration. Pharmacokinetic characteristics and tissue distribution of the preparation were determined by HPLC. The results were compared with those of normal β-elemene SLN (SLN-1) and elemene emulsion. Results After iv administration, the elimination half-life of FA-PEG-SLN in plasma was 44.0 min, significantly longer than that of SLN-1 and emulsions at 15.6 and 15.4 min. Compared with SLN-1, FA-PEG-SLN5min in the liver and kidney drug concentration is higher, slightly lower in the spleen. At 30 and 60 min, the concentration of β-elemene in FA-PEG-SLN group was significantly higher than that in SLN-1 group and emulsion group. Conclusion FA-PEG-SLN can circulate in the plasma for a long time, and its concentration in the main organs is higher and its elimination speed is slower, which has the value of further research.