Lee Chang-Moon, Choi Yongdoo, Huh Eun Jeong, Lee Ki Young, Song Ho-Chun, Sun Min Jung, Jeong Hwan-Jeong, Cho Chong-Su, Bom Hee-Seung
Interdisciplinary Program of Biomedical Engineering, Chonnam National University, Gwangju, Korea.
Cancer Biother Radiopharm. 2005 Dec;20(6):620-8. doi: 10.1089/cbr.2005.20.620.
Modification of liposomes using polyethylene glycol (PEG) results in steric hindrance to the phagocyte system and prolongation of blood circulation time. However, PEGylation can reduce radiolabeling efficiency (RE) when using the glutathione method for radiolabeling the liposomes. Therefore, we investigated the effect of the extent of PEGylation (PEG extent (PEGExt): 0, 5, 9.6, and 13.7 mol%) on the in vivo biodistribution of liposomes in Wistar rats, and RE with technetium-(99m) ((99m)Tc). PEGylated liposomes were prepared with egg phosphatidylcholine (egg PC, 1.85 mol%), cholesterol (1.0 mol%), and distearoylphosphatidylethanolamine-N-[polyethylene glycol] (DSPE-PEG; 0, 5, 9.6, and 13.7 mol%, respectively). The size distribution of the PEGylated liposomes was analyzed by a dynamic light scattering. The (99m)Tc-hexamethylpropylene-amine oxime ((99m)Tc-HMPAO) complexes were used for radiolabeling of preformed liposomes. The labeling efficiency and stability was analyzed with Sephadex G-15 column, and the biodistribution studies of (99m)Tc-liposomes after intravenous (i.v.) injection were also investigated with Wistar rats. The sizes of PEGylated liposomes decreased by increasing the PEGExt to 9.6 mol%, whereas sizes increased at 13.7 mol%. RE of (99m)Tc were greater than 90% for all PEGExt tested, and radiolabeling stability in human plasma was enhanced as a function of PEGExt. Liposomes without PEG were cleared rapidly from the blood and accumulated preferentially in the liver and the spleen. When PEGExt was increased, the accumulation in the organs decreased. This accumulation of PEG was maximized at 9.6 mol%. Accumulation of the liposomes in the spleen was increased again when PEGExt increased to 13.7 mol%. The splenic uptake of liposomes seemed to be dependent not only on PEGExt but also on the size of the liposomes. In conclusion, the PEG chains on the surface of liposome have no influence on the labeling efficiency, and the prolongation of circulation time was maximized at the 9.6 mol% of PEGylation.
使用聚乙二醇（PEG）修饰脂质体可对吞噬细胞系统产生空间位阻并延长血液循环时间。然而，在使用谷胱甘肽法对脂质体进行放射性标记时，聚乙二醇化会降低放射性标记效率（RE）。因此，我们研究了聚乙二醇化程度（PEG程度（PEGExt）：0、5、9.6和13.7摩尔%）对Wistar大鼠体内脂质体生物分布以及锝 -（99m）（（99m）Tc）放射性标记效率的影响。用蛋黄卵磷脂（蛋黄PC，1.85摩尔%）、胆固醇（1.0摩尔%）和二硬脂酰磷脂酰乙醇胺 - N - [聚乙二醇]（DSPE - PEG；分别为0、5、9.6和13.7摩尔%）制备聚乙二醇化脂质体。通过动态光散射分析聚乙二醇化脂质体的大小分布。用（99m）Tc - 六甲基丙烯胺肟（（99m）Tc - HMPAO）配合物对预先形成的脂质体进行放射性标记。用葡聚糖G - 15柱分析标记效率和稳定性，并用Wistar大鼠研究静脉注射（i.v.）后（99m）Tc - 脂质体的生物分布。随着PEGExt增加到9.6摩尔%，聚乙二醇化脂质体的尺寸减小，而在13.7摩尔%时尺寸增大。对于所有测试的PEGExt，（99m）Tc的放射性标记效率均大于90%，并且在人血浆中的放射性标记稳定性随PEGExt增加而增强。未修饰PEG的脂质体迅速从血液中清除，并优先在肝脏和脾脏中蓄积。当PEGExt增加时，在器官中的蓄积减少。这种聚乙二醇的蓄积在9.6摩尔%时达到最大。当PEGExt增加到13.7摩尔%时，脂质体在脾脏中的蓄积再次增加。脂质体在脾脏中的摄取似乎不仅取决于PEGExt，还取决于脂质体的大小。总之，脂质体表面的PEG链对标记效率没有影响，并且在聚乙二醇化程度为9.6摩尔%时，循环时间的延长达到最大。
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