Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
J Liposome Res. 2011 Mar;21(1):17-27. doi: 10.3109/08982101003699036. Epub 2010 Mar 24.
Efficient, convenient, and stable radiolabeling plays a critical role for the monitoring of liposome behavior via either blood sampling, organ distribution, or noninvasive nuclear imaging. The direct labeling of liposome-carrying drugs without any prior modification undoubtedly is convenient and optimal for liposomal drug testing. In this article, we investigated the effect of various lipid formulations and pH/chemical gradients on the radiolabeling efficiency and entrapment stability of technetium-99m ((99m)Tc) remotely loaded into liposomes, using (99m)Tc-N,N-bis(2-mercaptoethyl)-N',N'-diethyl-ethylenediamine ((99m)Tc-BMEDA) complex. The tested liposomes either contained unsaturated lipid or possessed various surface charges. (99m)Tc could be efficiently loaded into various premanufactured liposomes containing either an ammonium sulfate pH, citrate pH, or glutathione (GSH) chemical gradient. (99m)Tc-entrapment stabilities of these liposomes in phosphate-buffered saline (PBS; pH 7.4) buffer at 25°C were mainly dependent on the pH/chemical gradient, but not lipid formulation. Stability sequence was ammonium sulfate pH-gradient>citrate pH-gradient>GSH-gradient. Stabilities of (99m)Tc-liposomes in 50% fetal bovine serum (FBS)/PBS (pH 7.4) buffer at 37°C are dependent on both lipid formulation and pH/chemical gradient. Specifically, (99m)Tc labeling of the ammonium sulfate pH-gradient liposomes were less stable in 50% FBS/PBS than in PBS, whereas noncationic liposomes with citrate pH- or GSH-gradient displayed higher stability, except that anionic citrate pH-gradient liposomes showed no stability difference in these two media. Cationic liposomes aggregated in 50% FBS/PBS, forming a new discrete fraction with larger particle sizes. These in vitro characterization results have indicated the optimism of using (99m)Tc-BMEDA for labeling pH/GSH gradient liposomes without the requirement of modifying lipid formulation for liposomal therapeutic-agent development.
高效、便捷且稳定的放射性标记对于通过血液取样、器官分布或非侵入性核成像来监测脂质体行为至关重要。直接标记载药脂质体而无需任何预先修饰无疑是方便且优化的载药脂质体测试方法。在本文中，我们研究了不同脂质体制剂和 pH/化学梯度对远程加载到脂质体中的锝-99m（Tc-99m）（99mTc-BMEDA）复合物的放射性标记效率和包封稳定性的影响。测试的脂质体要么含有不饱和脂质，要么具有不同的表面电荷。Tc-99m 可以有效地负载到各种预制成的脂质体中，这些脂质体要么含有硫酸铵 pH 值、柠檬酸 pH 值或谷胱甘肽（GSH）化学梯度。在 25°C 的磷酸盐缓冲盐水（PBS；pH 7.4）缓冲液中，这些脂质体中 99mTc 的包封稳定性主要取决于 pH/化学梯度，而与脂质体制剂无关。稳定性顺序为硫酸铵 pH 梯度>柠檬酸 pH 梯度>GSH 梯度。在 37°C 的 50%胎牛血清（FBS）/PBS（pH 7.4）缓冲液中，99mTc-脂质体的稳定性取决于脂质体制剂和 pH/化学梯度。具体而言，在 50%FBS/PBS 中，与在 PBS 中相比，硫酸铵 pH 梯度脂质体的 Tc-99m 标记稳定性较低，而具有柠檬酸 pH 梯度或 GSH 梯度的非阳离子脂质体显示出更高的稳定性，但带负电荷的柠檬酸 pH 梯度脂质体在这两种介质中没有稳定性差异。阳离子脂质体在 50%FBS/PBS 中聚集，形成具有更大粒径的新离散部分。这些体外特性研究结果表明，使用 99mTc-BMEDA 对 pH/GSH 梯度脂质体进行标记而无需修饰脂质体制剂对于开发治疗性载药脂质体是乐观的。
