Anderson Michael, Paradis Céline, Omri Abdelwahab
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada.
Drug Deliv. 2003 Jul-Sep;10(3):193-200. doi: 10.1080/713840396.
In this study, the blood clearance and organ distribution of intravenously administered liposomes (distearoyl phosphatidylcholine [DSPC] and cholesterol in a ratio of 3:1) was evaluated by utilizing 3H-cholesteryl ether as the lipid phase marker. Also, the ability of liposomes, as a drug delivery system, to alter the distribution and retention of encapsulated agents was investigated by comparing the distribution of intravenously administered free and liposome-encapsulated 14C-inulin within a 48-hr postadministration period. Intravenously administered DSPC liposomes were distributed in all organs examined with the highest levels of 3H-cholesteryl ether and 14C-inulin present in the liver and spleen; peak levels occurred 3 hr postadministration (71.86% +/- 9.39 versus 77.67% +/- 10.30, respectively, in the liver and 5.05% +/- 1.07 versus 5.36% +/- 1.09, respectively, in the spleen) declining gradually during the remaining experimental period. The lowest levels of 3H-cholesteryl ether and 14C-inulin following administration of liposome-encapsulated inulin were found in the lung, kidney, and heart. The area under curve showed much more accumulation of 14C-inulin (6-fold higher) in the body following administration of the liposome-encapsulated drug than the free drug. The ratio of 3H to 14C following administration of liposome-encapsulated inulin was constant throughout the entire observation period, suggesting that the disposition of inulin acquired both the carrier's rate of clearance and tissue distribution. These results indicated that following intravenous administration of liposome-encapsulated inulin, the majority of the radioactively labeled formulation was retained by the organs of the reticuloendothelial system (liver and spleen); liposomes greatly enhanced the retention of inulin in the body; and the liposomal formulation did not destabilize and subsequently did not release the encapsulated inulin to the tissues and organs.
在本研究中，通过使用³H-胆固醇醚作为脂质相标记物，评估了静脉注射脂质体（二硬脂酰磷脂酰胆碱[DSPC]与胆固醇比例为3:1）的血液清除率和器官分布。此外，通过比较静脉注射游离的和脂质体包裹的¹⁴C-菊粉在给药后48小时内的分布情况，研究了脂质体作为药物递送系统改变包裹药物分布和滞留的能力。静脉注射的DSPC脂质体分布于所有检测的器官，肝脏和脾脏中³H-胆固醇醚和¹⁴C-菊粉的含量最高；给药后3小时达到峰值水平（肝脏中分别为71.86%±9.39%和77.67%±10.30%，脾脏中分别为5.05%±1.07%和5.36%±1.09%），在剩余实验期间逐渐下降。脂质体包裹菊粉给药后，³H-胆固醇醚和¹⁴C-菊粉在肺、肾和心脏中的含量最低。曲线下面积显示，给药脂质体包裹药物后，¹⁴C-菊粉在体内的蓄积量比游离药物高6倍。脂质体包裹菊粉给药后，³H与¹⁴C的比值在整个观察期内保持恒定，表明菊粉的处置获得了载体的清除率和组织分布。这些结果表明，静脉注射脂质体包裹菊粉后，大部分放射性标记制剂被网状内皮系统器官（肝脏和脾脏）保留；脂质体大大增强了菊粉在体内的滞留；并且脂质体制剂没有不稳定，随后也没有将包裹的菊粉释放到组织和器官中。
