掺入不同形式PEG的大黄素脂质体大鼠体内药动学过程

Pharmacokinetics of emodin liposomes mixed with different forms of PEG in rats

目的:考察mPEG-Emo-Lip,DSPE-Emo-Lip,Chol-Emo-Lip 3种掺入不同形式PEG的大黄素脂质体在大鼠体内的药动学过程。方法:采用薄膜分散-超声法制备m PEG-Emo-Lip,DSPE-Emo-Lip,Chol-EmoLip 3种脂质体;经大鼠尾静脉注射给药,HPLC法测定大黄素的血药浓度,拟合药动学方程,比较3种脂质体的长循环效果。结果:与Emo-Lip相比,m PEG-Emo-Lip,DSPE-Emo-Lip,Chol-Emo-Lip的消除半衰期(t1/2)分别为(2.29±0.32),(4.25±0.76),(3.36±0.47)倍,平均滞留时间(MRT)分别为(1.72±0.26),(3.52±0.61),(2.42±0.31)倍,药时曲线下面积(AUC)分别为(2.23±0.06),(5.30±0.28),(3.83±0.34)倍,血浆清除率(CL)分别为(0.44±0.01),(0.19±0.01),(0.26±0.02)倍。结论:掺入m PEG2000,DSPEPEG2000,Chol-PEG2000 3种形式PEG的大黄素脂质体能够延长消除半衰期和平均滞留时间,显示体内长循环效应,其中DSPE-Emo-Lip的长循环效果更为显著。

Objective： To study the pharmacokinetics of emodin liposomes mixed with m PEG2000,DSPEPEG2000 or Chol-PEG2000 in rats. Methods： m PEG-Emo-Lip,DSPE-Emo-Lip and Chol-Emo-Lip were prepared by film-ultrasonic dispersion. The emodin liposomes were injected to rats through caudal vein. HPLC method was established to determine the concentrations of emodin in plasma samples,and then the kinetic equations were used to fit the pharmacokinetics of emodin liposomes in rats. The long-circulation effects of the three forms of emodin liposomes were compared. Results： Compared to Emo-Lip,the elimination half-lives（ t1/2） of m PEG-Emo-Lip,DSPE-Emo-Lip and Chol-Emo-Lip were extended by（ 2. 29 ± 0. 32）,（ 4. 25 ± 0. 76） and（ 3. 36 ± 0. 47） folds,the mean residence time（ MRT） was increased by（ 1. 72 ± 0. 26）,（ 3. 52 ± 0. 61） and（ 2. 42 ± 0. 31） folds,the areas under the concentration-time curve（ AUC） were increased by（ 2. 23 ± 0. 06）,（ 5. 30 ± 0. 28） and（ 3. 83 ±0. 34） folds,and the clearance（ CL） in plasmas was decreased by（ 0. 44 ± 0. 01）,（ 0. 19 ± 0. 01） and（ 0. 26 ±0. 02） folds,respectively. Conclusion： Emodin liposomes mixed with m PEG2000,DSPE-PEG2000 or Chol-PEG2000 can prolong the t1/2and MRT,which demonstrate long-circulation effects. The DSPE-Emo-Lip shows more obvious long-circulation effect.