Ishida O, Maruyama K, Sasaki K, Iwatsuru M
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
Int J Pharm. 1999 Nov 10;190(1):49-56. doi: 10.1016/s0378-5173(99)00256-2.
We have examined the size dependence of extravasation and interstitial localization of polyethyleneglycol-coated liposomes (PEG-liposomes) in the solid tumor tissue by means of electron microscopic observation. Liposomes composed of distearoyl phosphatidylcholine, cholesterol and distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared in various size ranges. PEG-liposomes with an average diameter of 100-200 nm showed the most prolonged circulation time and the greatest tumor accumulation in all the solid tumors employed in this experiment. Although large PEG-liposomes with a diameter of 400 nm showed a short circulation time in normal mice, the results in splenectomized mice indicated that they do have an intrinsic prolonged circulation character in vivo. However, large PEG-liposomes could not extravasate into solid tumor tissue. These results indicate that the size of liposomes is critical for extravasation. The electron microscopic observations revealed the almost exclusive engulfment of extravasated liposomes by tumor-associated macrophages; very few were taken up by tumor cells.
我们通过电子显微镜观察，研究了聚乙二醇包被脂质体（PEG脂质体）在实体瘤组织中的渗出及间质定位的尺寸依赖性。制备了由二硬脂酰磷脂酰胆碱、胆固醇和聚乙二醇（PEG）的二硬脂酰磷脂酰乙醇胺衍生物组成的不同尺寸范围的脂质体。在本实验所用的所有实体瘤中，平均直径为100 - 200 nm的PEG脂质体显示出最长的循环时间和最大的肿瘤蓄积。虽然直径为400 nm的大PEG脂质体在正常小鼠中循环时间较短，但脾切除小鼠的结果表明它们在体内确实具有内在的延长循环特性。然而，大PEG脂质体不能渗出到实体瘤组织中。这些结果表明脂质体的尺寸对于渗出至关重要。电子显微镜观察显示，渗出的脂质体几乎完全被肿瘤相关巨噬细胞吞噬；很少被肿瘤细胞摄取。
