羟基喜树碱长循环亚微乳的制备及其在大鼠体内的药动学

Preparation of Long Circulation Submicron Emulsions Loaded with Hydroxycamptothecin and Its Pharmacokinetics in Rats

以二硬脂酰磷脂酰乙醇胺-聚乙二醇(DSPE-PEG)2000共聚物、大豆磷脂S75、硬脂酰胺、泊洛沙姆188为辅料制备羟基喜树碱长循环亚微乳,所得长循环亚微乳平均粒径为(170.7±10.0)nm,ζ电位为(28.98±1.06)mV。同法制备了未PEG修饰的亚微乳。以喜树碱为内标,采用HPLC法测定血浆中的药物浓度。大鼠分别单剂量尾静脉注射给予羟基喜树碱长循环亚微乳、未PEG修饰的亚微乳和注射液。药动学研究表明,长循环亚微乳的t1/2β和MRT均较未修饰亚微乳和注射液显著延长,提示PEG修饰的亚微乳在体内有较好的长循环作用。

The long circulation submicron emulsions loaded with hydroxycamptothecin were prepared with distearoylphosphatidylethanolamine-PEG 2000 （DSPE-PEG 2000）, soybean phospholipid S75, stearylamine and Poloxamer 188 as excipients. The droplet size and ξ potential of the long circulation submicron emulsions were （170.7± 10.0）nm and （28.98±1.06） mV. The submicron emulsions loaded with hydroxycamptothecin were also prepared without DSPE-PEG 2000. The drug concentration in rat plasma was determined by HPLC with camptothecin as internal standard. The long circulation submicron emulsions, submicron emulsions and injection were administrated with a single dose of 4 mg/kg via caudal vein, respectively. The results showed that t1/2β and MRT of the long circulation submieron emulsions were significantly longer than those of submicron emulsions and injection. It indicated that the PEGylated submicron emulsions had a better long-circulating effect in rats.